|Title of Invention||
PHOTOSTABLE CATIONIC ORGANIC SUNSCREEN COMPOUNDS WITH ANTIOXIDANT PROPERTIES AND COMPOSITIONS OBTAINED THEREFROM
|Abstract||A compound of Formula 1 wherein R is methoxy, or one R is H and other R is methoxy; R1 is selected from the group consisting of COCH3, CO2R5, CONH2,CONH(R6)2,CN,COX(CH2)n-N-(R2)(R3), and the quaternized salt form of the formula COX(CH2)n-N-(R2)(R4)(R3)+; X is O or NH; n is an integer of 1 to 5; Y is an anion; R2, R3 and R4 are independently linear or branched C1 to C20 alkyl; and R5 and R6 are independently hydrogen or linear or branched C1- C20 alkyI.|
|Full Text||BACKGROUND OF THE INVENTION
Photofilters and UV-absorbers have been employed for a number of years
to protect coloring dyes from fading from exposure to light. UV-sunscreens
have also been employed to protect skin from damage from exposure to
sunlight. Representative references related to UV-sunscreens are:
U.S. Patent No. 5,922,310 (Chaudhuri et al.) discloses a composition which
includes a cationic antioxidant phenol in an amount of about 0.01-1% wt/wt.
U.S. Patent No. 5,427,773 (Chaudhuri et al.); U.S. Patent No. 5,427,774
(Chaudhuri et al.); and U.S. Patent No. 5,451,394 (Chaudhuri et al.)
discloses non-hydrolysable, non irritating, hair, skin and textile substantive
quaternary salts of p-dialkylaminobenzamides.
U.S. Patent No. 5,633,403 (Gallagher et al.) discloses substantive UV-
absorbing cinnamido amine cationic quaternary salts.
U.S. Patent No. 5,830,441 (Wang et al.) discloses a photostable UV
absorbent with maximum absorption above 340 nm.
Hair is largely comprised of polypeptide chains that are held together by
disulfide bonds which link adjacent polypeptide chains. The disulfide bonds
are largely responsible for the mechanical strength and extensibility of hair.
Exposure to sun tends to cause these disulfide bonds to break making the
hair stiff and brittle in dry weather and frizzy in humid weather. Additionally,
the hair also loses its color and luster in such conditions.
The essential first event in hair photo damage, as in all processes, is light
absorption by the Fiber. Only wavelengths above 290 nm will be
consequential in natural photo damage since shorter wavelength UV light
the stratosphere will effectively filter out. The most significant
chromophores in proteins that absorb in the UV-B region are the amino
acids, tyrosine (λmax 275 nm), tryptophan (λmax 280 nm), and the disulfide
bonds (weak absorption at 290 nm). The longer wavelength UV-A and the
visible light are not likely to cause damage directly since proteins do not
absorb them. However, UV-A light is well known for generating free
radicals; consequently damage to cholesterol and fatty acids occur.
The photodegradation of hair results in a variety of physical and chemical
changes. Among the physical changes are elimination of cuticle cells,
roughening of the hair surface, loss of mechanical and elastic strength, and
increased porosity. Chemically, we find photooxidation of cysteine,
cholesterol, and fatty acids; the decomposition of tryptophan; breakage of
disulfide bonds; and bleaching of melanin and artificial hair colors can
Human hair damage caused by sunlight in the UV spectrum is more severe
than that resulting from all other factors such as weather, wind, atmospheric
pollution, salt water, chlorinated water, perming, coloring, bleaching and
improperly applied or repetitive treatments. Sunscreens used for skin are
not suitable for hair because they are either not substantive or leave the
hair dull and tacky. For hair protection, several approaches have been
described, such as the deposition of photofilters on the hair surface, and
the use of antioxidants or free radical scavengers.
Recently, sunscreens also have been added to hair care products to guard
against the deleterious effects of solar irradiation on the hair. Two
sunscreens have been developed especially for hair, Escalol® HP 610 (US
5,451,394) and Incroquat® UV-283 (US 5,633,403). Unfortunately, they
both suffer from inadequate photostability, meaning that they degrade in
the presence of light, and they lack desired hair substantivity, meaning that
they can not be effectively applied and retained on hair.
The ideal sunscreen formulation for hair should be nontoxic and non-
irritating to the skin tissue and be capable of convenient application in a
uniform and continuous film. The product should be chemically and
physically stable so as to provide an acceptable shelf life upon storage. It
is particularly desirable that the preparation should retain its protective
effect over a prolonged period after application. The product must be
substantive to hair or skin so that it does not get washed-off quickly. Thus,
the active agent when present on the hair or skin must be resistant to
chemical and/or photodegradation and be substantive.
Techniques for stabilizing UV absorbent compositions are known.
Representative disclosures in this area include U.S. Patent Nos. 5,567,418,
5,538,716, 5.951,968 and 5,670,140.
Antioxidants are believed to function by providing protection from free-
radical damage. To be an effective free radical quencher, it is believed the
antioxidant must be present in an adequate concentration at the site of free
radical generation. Since antioxidants are used in low concentrations and
typically lack functionality to become substantive to hair or skin, they may
not be available at the site of generation, thereby reducing the desired
protection. Many existing antioxidants can also act as pro-oxidants instead
of antioxidants in presence of iron and copper (see a review on Transition
Metal-Induced Oxidation by Chaudhuri and Pucceti, Cosm & Toil, Vol 117,
No. 9, p.43-56", 2002). Based on these beliefs, it is desirable to provide the
antioxidant (having no pro-oxidation activity induced my transition metals)
and photostable sunscreen functionality in a single molcule which is
substantive to hair, skin or other substrates to enhance the effectiveness of
the antioxidant properties.
SUMMARY OF THE INVENTION
There is provided by the present invention compounds with sunscreen
activity, i.e. they are chromophoric within the ultra violet radiation range of
from 290-400 nm and they also exhibitantioxidant properties. The
sunscreen Tormulations of this invention preferably offer protection from UV
radiation with wavelengths of about 290 nm to 400 nm and preferably from
wavelengths in the range of about 290-370 nm.
The compounds of the invention herein are represented by the general
In Formula I, each R is independently linear or branched C1 to C8 alkyl, or
linear or branched C1 to C8 alkoxy; or one R is H and the other R is linear or
branched C1 to C8 alkyl, or linear or branched C1 to C8 alkoxy.
R1 is selected from the group consisting of COCH3, CO2R5, CONH2,
CONH(R6)2, CN, COX(CH2)n-N-(R2)(R3), and the quatemized salt form
of the formula COX(CH2)n-N-(R2)(R4)(R3)
X is O or NH;
n is an integer of 1 to 5;
Y is an anion;
R2, R3 and R4 are independently linear or branched C1 to C20 alkyl; and
R5 and R6 are independently hydrogen or linear or branched C1-C20 alkyl.
Preferred compounds of Formula I for hair and other substrate protection
are illustrated by Formula II
In Formula II, Ri is as defined for Formula I but is preferably COCH3 or
CONH(CH2)3N+(CH3)2(CH2CH3) CH3CH2OSO'3; and X is O or NH.
Concerning Formulae I and II, the integer n is preferably 2 to 3; and the
anion Y is preferably CI, Br, alkyl sulfate, alkyl sulfonate, or p-tolyl
sulfonate. R2, R3 and R4 of formulae I and II are preferably independently
linear or branched C1 to C8. R5 and R6 are preferably C1 to C8 alkyl.
The invention is also directed to a hair care formulation containing the
compound of the invention. The compound is typically used as a protective
and conditioning ingredient in the hair care formulation against UV-A rays,
UV-B rays, or both against UV-A and UV-B rays. The formulation can
contain a single compound of formula I or a mixture of compounds of
Preferably, the hair care formulation contains a compound or a mixture of
compounds of the invention which are substantive and capable of
protecting hair, skin or fibers against illumination in the range of about 310
to 360 nm.
It is also preferable that the compound or a mixture of compounds of the
invention be capable of stabilizing the hair care formulation against
photodegradation, and be further capable of providing an antioxidant
property to the formulation.
In another aspect, the invention is directed to a mixture containing at least
one compound of the invention and at least one other sunscreen agent.
Advantageously, the other sunscreen agent is a sunscreen agent not of
Formula I, and the compound of the invention is capable of stabilizing the
additional sunscreen agent against photodegradation, or is capable of
providing an antioxidant property to the mixture.
In yet another aspect, the invention is also directed to a method of
protecting a substrate from UV radiation by applying a compound or mixture
of compounds of this invention to the substrate.
Advantageously, the substrate protected from UV radiation is hair.
Alternatively, the substrate protected from UV radiation is a polymer, textile
fabric, leather or paint. Alternatively, the compound can be used with a
hairpiece made of natural or synthetic hair to protect the hairpiece from
When the substrate is hair, an amount of the compound sufficient to
improve the photostability of the hair care formulation is preferably added,
and advantageously, in an amount sufficient to improve the antioxidant
The compounds of this invention can also be used for improving the
photostability of a U.V. absorbing composition by adding an effective
amount of the compound. Likewise, the antioxidant activity of a
composition can be improved by adding an effective amount of a
compound of this invention with antioxidant activity. The composition can
have one or more compounds of the invention and additional sunscreen
agents which are not of the invention.
The sunscreen formulations may contain dispersing agents, emulsifiers or
thickening agents to assist in applying a uniform layer of the active
compounds. Suitable dispersing agents for the sunscreen formulations
include those useful for dispersing organic or inorganic sunscreen agents in
either a water phase, oil phase, or part of an emulsion, including, for
Emulsifiers may be used in the sunscreen formulations to disperse one or
more of the compounds or other components of the sunscreen formulation.
Suitable emulsifiers include conventional agents such as, for example,
glycerol stearate, stearyl alcohol, cetyl alcohol, dimethicone copolyol
phosphate, hexadecyl-D-glucoside, octadecyl-D-glucoside, etc.
Thickening agents may be used to increase the viscosity of the sunscreen
formulations. Suitable thickening agents include carbomers,
acrylate/acrylonitrile copolymers, xanthan gum and combinations of these.
The carbomer thickeners include the crosslinked CARBOPOL® acrylic
polymers from B.F. Goodrich. The amount of thickener within the
sunscreen formulation, on a solids basis without water, may range from
about 0.001 to about 5%, preferably from 0.01 to about 1% and optimally
from about 0.1 to about 0.5% by weight.
Minor optional adjunct ingredients for the sunscreen formulations to be
applied to skin or hair may include preservatives, waterproofing agents,
fragrances, anti-foam agents, plant extracts (Aloe vera, witch hazel,
cucumber, etc) opacifiers, skin conditioning agents and colorants, each in
amounts effective to accomplish their respective functions.
The sunscreen formulations may optionally contain an ingredient which
enhances the waterproof properties such as, compounds that form a
polymeric film, such as dimethicone copolyol phosphate, diisostearoyl
trimethyolpropane siloxysilicate, chitosan, dimethicone, polyethylene,
polyvinylpyrrolidone (PVP), polyvinylpyrrolidone/vinylacetate, PVP/Eicosene
copolymer and adipic acids/diethylene, glycol/glycerine crosspolymer etc.
Waterproofing agents may be present at levels of from about 0.01 to about
10% by weight.
The sunscreen formulations may optionally contain one or more inorganic
sunscreen agents as discussed above including micro fine surface treated
titanium dioxide and micro fine untreated and surface treated zinc oxide.
Titanium dioxide in the sunscreen compositions preferably has a mean
primary particle size of between 5 and 150 nm and preferably from 10 to
100 nm. Titanium oxide may have anatase, rutile or amorphous structure.
The zinc oxide in the sunscreen compositions preferably has a mean
primary particle size of between 5 nm and 150 nm, preferably between 10
nm and 100 nm. Examples of modified titanium dioxide compositions
include (but not limited to only one supplier):
Eusolex® T-45D (surface treated with alumina and simethicone, 45%
dispersion in isononoyl isononoate);
Eusolex®T-Aqua, (surface treated with aluminum hydroxide, 25%
dispersion in water);
Eusolex® TS (surface treated with aluminum stearate)
Eusolex® T-2000 and Eusolex® T-ECO (surface treated with alumina and
simethicone), all available from MERCK KGaA.
The sunscreen formulation may also contain one or more additional
monomeric organic chromophoric compounds. These can either be UV-A,
UV-B or broad band filters. Examples of suitable UV-A sunscreens include
benzophenone derivatives, menthyl anthranilate, butyl methoxydibenzoyl
methane and benzylidene-dioxoimidazoline derivatives. Examples of
suitable UV-B sunscreens include cinnamate derivatives, salicylate
derivatives, para-aminobenzoic acid derivatives, camphor derivatives,
phenylbenzimidazole derivatives and diphenytacrylate derivatives.
Examples of suitable broad-band sunscreen include benzotriazole
derivatives and triazine derivatives such as anisotriazone. Others include
ethylhexyttriazone and diethylhexylbutamidotriazone.
Particularly useful organic sunscreen agents that can be introduced are
Avobenzone, 2-ethylhexyl p-methoxycinnamate, 4,4'-t-
butylmethoxydibenzoyl methane, 2 hydroxy-4-methoxybenzophenone,
octyldimethyl p-aminobenzoic acid, 2,2-dihydroxy-4-
methoxybenzophenone, ethyl-4-[bis(hydroxypropyl)]aminobenzoate, 2-
ethylhexyl-2-cyano-3,3-diphenylacrylate, 2-ethylhexylsalicylate, glycerol p-
aminobenzoate, 3,3,5-trimethylcyclohexylsalicylate, methylanthranilate, p-
dimethylaminobenzoic acid, 2-ethylhexyl p-dimethylaminobenzoate, 2-
phenylbenzimidazole-5-5-sulfonic acid, 2-(p-dimethylamino phenyl-5-
sulfoniobenzoxazoic acid and mixtures thereof.
Examples of useful commercially available organic sunscreen agents that
can be introduced include 2-phenylbenzimidazole-5-sulphonic acid, 2-(4-
methylbenzylidene)-camphor, 4-isopropyldibenzoyl methane all of the
Eusolex™ series sold by EM Industries and Merck KGaA, Darmstadt,
Although not preferred, the sunscreen formulation may contain an
additional antioxidant. Examples of suitable antioxidants which provide
stability include p-hydroxybenzoic acid and its derivatives (ethylisobutyl,
glyceryl esters of p-hydroxybenzoic acid); coumarin derivatives; flavones;
hydroxy or methoxy substituted benzophenones; uric or tannic acid and its
In addition to providing sunscreen activity at levels which provide U.V.
absorption, the compounds of Formula I can be introduced into a hair care
formulation at levels which provide antioxidant activity. It has been found
that to provide antioxidant functionality, the phenyl group of the compounds
of formula I should have a substituent pattern of "3, 5-alkoxy, 4-hydroxy."
Compounds of formula I and II also have a moiety which provides UV
absorbing functionality, (chromophoric in the UV range).
Additionally, the following compounds can be obtained:
wherein R = linear or branched C1-C8 alkyl or linear or branched C1-C8
alkoxy or one R is H and the other R is linear or branched C1 to C8 alkyl, or
linear or branched C1 to C8 alkoxy, with a compound that provides a
terminal tertiary amine. An example of a compound that provides a
terminal tertiary amine is a compound of the formula: R1-CH2-C(O)X (CH2)n-
N(R2)(R3) wherein R1- R3 and X are as defined above for formula I. The
tertiary amine is then quarternized with a salt of the formula (R4)Y, wherein
R4 is as defined above for formula I. An example of a suitable salt is
The corresponding benzaldehyde can be obtained commercially or
prepared from 3, 4, 5-trimethoxybenzaldehyde through selective
monodemethylation at the 4-position. This technique leads to
syringaldehyde. Alternately, syringaldehyde or other substituted aldehydes
can be prepared from 3-bromo-4-hydroxy-5-methoxybenzaldehyde (5-
Bromo vanillin) by replacing the bromo atom with methoxy (or alkoxy) using
the appropriate alcohol.
Although not wishing to be bound by any specific theory, it is believed that a
representative Reaction I resulting in a compound of formula I proceeds in
a manner such as this:
Wherein "R7" is C1-C20 linear or branched alkyl, such as ethyl, iso-amyl and
ethylhexyl, and R1 is as defined above for formula I.
Similarly, a compound of Formula I has been synthesized from the following
representative Reaction II, wherein the condensation step is followed by a
The tertiary amine can be quaternized with diethylsulfate, p-toluene
sulfonate or other salts such as C12H25 mesylate,
wherein R is as defined above for formula I such as methoxy and t-butyl
and R is as defined above for Representative Reaction I. An example of a
quaternization reaction which provides a compound of formula IV is
The compounds described above and hair care compositions comprising at
least one of these compounds are useful to reduce artificial hair color
fading and to protect artificial colored hair from fading. This protection is for
example advantagous during hair wash. Therefore the compound is in one
preferred embodiment of the invention used as an additive for shampoo-
based formulations. Furthermore the compounds and hair care
compositions comprising at least one the compounds are useful to reduce
cleavage of disulfide bonds in hair and to to protect hair protein disulfide
bonds from cleavage.
The entire disclosure of all applications, patents and publications, cited
above are hereby incorporated by reference.
The examples below provide guidelines on how to make representative
compounds of the invention.
This process is taken in two steps.
1) Selective demethylation
Momodemethylation of 3,4,5, trimethoxy benzaldehyde is performed using
sulphuric acid at 40 degrees for 8 hours. Syringaldehyde is yielded.
N,N-Dimethylaminopropyl-alpha-cyanoacetamide is yielded at 80-85% by
amidation of ethyl cyanoacetate using dimethyl aminopropylene in neat
condition at 90-95'C.
3,5-Dimethyl-4-hydroxy benzaldehyde (Syringaldehyde) is condensed with
N.N-Dimethylaminopropyl-alpha-acylacetamide in the presence of
piperdine-acetic acid and benzene as media at reflux temperature under
continuous azeotropic water removal to yield the title compound. The
reaction takes about 2 hours for completion. The yield obtained is about
The compound is a hair care sunscreen with antioxidant properties and can
be quatemized with diethylsulfate to provide a substantive hair care
sunscreen with antioxidant properties.
The process involves 3 steps:
1) Selective demethylation
Monodemethylation of 3, 4,5, trimethoxy benzaldehyde is performed using
sulphuric acid at 40 degrees C for 8 hours. Syringaldehyde is yielded.
The N,N-Dimethylaminopropyl-alpha-cyanoacetamide is yielded at 80-85%
by amidation of ethyl cyanoacetate using dimethyl aminopropylene in neat
condition at 90-95°C.
3,5-diimethoxy-4-hydroxy benzaldehyde is condensed with N.N-
Dimethylaminopropyl-alpha-cyanoacetamide in the presence of piperdine-
acetic acid and benzene as media at reflux temperature under continuous
azeotropic water removal. N-(3-Dimethylaminopropyl)-alpha-cyano-3,5-
dimethoxy-4-hydroxy cinnamide is yielded. The reaction takes two hours
for completion. The yield is 90%.
The N-(3-Dimethylaminopropyl)-alpha-cyano-3,5-dimethoxy cinnamide is
quaternised with dodecyl mesylate (C12H25OSO2CH3) at 100-105 degrees C
in propylene glycol as a reaction medium. The final compound is produced
with a 92% yield.
malonamide bis ethylsulfate
malonamide bis ethylsulfate is prepared by condensation of 3,5-dimethoxy
4-hydroxy benzaldehyde and bis-N-[3-(N,N-
dimethylamino)propyl]malonamide according to the following reaction
scheme and procedure:
piperidine (3.95 ml) and acetic acid (7.90); are heated to reflux temperature
and stirred with continuous water removal for 13.5 hours. The reaction was
checked by TLC (mobile phase= benzene:hexane:acetone (80:20:10)) with
product detected under UV. Once product is detected, the reaction mass is
cooled to 60-65 deg. C. and benzene removed under mild vacuum at 60-80
deg. C. The mass is degassed for 1/2 hour under vacuum at 75-80deg.C.
and nitrogen bleeding is started. The thick residue is dissolved in dimethyl
formamide (200.0ml) with stirring and cooled to 10-15 deg C.
The dissolved reaction mass is charged with diethyl sulphate (150.0 gm) at
10-15 deg C and is heated to 85-90 deg. C. with stirring for six hours.
Benzene (400.0ml) is charged into this mixture and stirred for 10 minutes at
85-90 deg. C, after which, separate layers were allowed to form. The
product layer (lower layer) was separated and washed with benzene (250
ml) at 85-90 deg. C, charged with methanol (350 ml) and charcoal (10.0
gm) at 50-55 deg. C. with stirring for one hour and then filtered through a
Hydro-flow bed. The filtered layer was washed with methanol (50 ml) and
distilled at 50-55 deg. C. with vacuum to remove methanol.
The mass was degassed for one hour at 90-95 deg. C. under vacuum. The
yield obtained is about 85%. The product is highly soluble in water and has
λmax 323 nm (EtOHrwater- 70%:30%) with εmax = 10,500 cm-1 mol-1. A 50%
solution in water was prepared for ease of handling.
malonamide bis ethylsulfate
This material was prepared by following the procedure described in
Example 3, except syringaldehyde was replaced with vanillin as a starting
material. The product has a λmax at 334 nm (e max 18050 cm"1 mol-1). A
50% solution in water was prepared for ease of handling.
DPPH Test Method
A DPPH concentrate (2.5X) of 25mg of 1,1-Diphenyl-2-Picyrl-Hydrazyl
ACS# 1898-66-4 (Sigma #D-9132, lot 99H3601) dissolved in 250mL
ethanol (USP), is prepared fresh on the measurement date. A DPPH
working solution is then prepared by diluting 100mL of this concentrate to a
final volume of 250mL (100 M/mL). A blank 13x100mm borosilicate glass
screw top tube of ethanol (USP) is used to zero the spectrometer (Milton
Roy, Spectronic 20+) at 517 nm and a control tube of DPPH working
solution is measured under identical conditions, and taken as 0% activity.
Aliquots of the 0.25% & 0.5% (RT & 45EC) test solution are added to tubes
followed by the rapid addition of 4mL DPPH working solution then rapidly
capped and mixed. After 20 minutes, the absorbance of each sample is
read at 517 nm.
The percent reducing activity (%RA) is calculated using the following
% Reduction Activity = 100 A (0)-A(20)
Where A(0) is the absorbance value of the DPPH working solution at
517nm zeroed against an ethanol blank and A(20) is the absorbance at
517nm, 20 minutes after combining the antioxidant with the DPPH working
The concentration of antioxidant (mg/ml) in the final assay mixture is
calculated based on the dilution of respective aliquots of each compound in
the final assay volume and %RA tabulated and plotted as percent activity at
each concentration in the dilution series.
Compounds with 3,5-dimethoxy-4-hydroxy substitution are found to exhibit
much higher reducing activity (antioxidant activity) than compounds with
3,4,5-trimethoxy substitution. In order to boost antioxidant activity of the
compounds of the present invention, other antioxidants can be combined.
Some examples are those antioxidants mentioned above are Tocopherols,
tocopherylacetate, Ascorbic acid, Emblica antioxidants, Proanthocyanidins
(from pine bark, grape seed extract, and the like) green tea polyphenols,
rosemary antioxidants, gallic acid, ellagic acid, butylhydroxy toluene (BHT),
butylhydroxy anisole (BHA) and the like.
Antioxidant activity of some of the product in the present invention is
included in Table A which follows:
The photostability of compounds of the present invention as well as existing
commercial cationic sunscreens is tested according to the procedure
Photostability: Comparative Photostability of Example 3, Incroquat® 283
and Escalol® HP610
Three products [Example 3 (1%), Incroquat 283 (1%) and HP610 (0.1%)]
were tested for their photostability by dissolving separately in water or
ethanol-water solution containing 0.1% Poly(vinylpyrrolidone-vinyl acetate)
copolymer (PVP-VA S630 from ISP). Air drying on a glass plate for one
hour gave a thin film, which were irradiated under UV A (2 MED/h) and UV
B (1 MED/h) light separately over an 8h period in a Q-UV Accelerated
Weathering Tester. Photodegradation was calculated from the decrease in
the maximum absorption of the respective products. The results are
illustrated in Figures 1 and 2.
The results in Figures 1 and 2 clearly show that the product obtained from
Example 3 has much higher photostability over the two commercially
available cationic sunscreens, namely, Escalol® HP 610 and Incroquat®
The stabilizing activity of the compound obtained from Example 3 toward
Avobenzone is tested and compared with a conventional product according
to the procedures below.
Two formulated products [one containing Avobenzone (2%w/w) and the
other one with Avobenzone+Example 3 product (2+2% w/w)] were tested
for their photostability by applying samples (1-2 ng/cm2) in between two
glass plates and irradiating the samples under UV A (2 MED/h) and UV B
(1 MED/h) light separately over a 6hour period in a Q-UV Accelerated
Weathering Tester. Photodegradation was calculated from the decrease in
the maximum absorption of the respective products. The results show a
54% improvement in photostabilization of Avobenzone using Example 3
Hair Substantivity: Comparative hair substantivity of Example 3, Incroquat®
283 and Escalol® HP610
Tests in aqueous solution: Tests are performed by using aqueous solutions
of Example 3 and Incroquat at 1% concentration. 100 ml aqueous solution
(containing 100 mg product) are added, under constant stirring, to 1g of a
slightly bleached hair swatch (cut in fine pieces less than 1/3 " long). The
product uptake is determined by measuring the maximal absorption of
product remaining in the solute over time. The results for Example 3 and
Incroquat at 1% concentration are shown in Figure 3. Escalol® HP610
could not be tested in aqueous solution due to its very poor solubility.
Test in aqueous ethanolic solution: Example 3 and Incroquat® UV 283
have been prepared in aqueous-ethanolic solution (30:70%) at 1%
concentration while a maximal concentration of Escalol® HP610 was
reached at 0.25%. 100 ml of each solution is added, under constant stirring,
to 1 g of a slightly bleached hair swatch under identical conditions as the
previous test. The values for relative uptake of these solutions are reported
in Figure 4.
For better comparison, the relative uptake of Escalol® HP610 is corrected
from 0.25% solution to a 1 % solution to account for the same initial weight
amount as compared to the other two cationic sunscreens (100 mg of initial
The results illustrated in Figure 4 clearly show that the product obtained
from Example 3 has much higher hair substantivity from both aqueous and
aqueous-ethanolic solutions over two commercially available cationic
sunscreens, namely, Escalol® HP 610 and Incroquat® UV 283.
Iron-catalyzed formation of a hydroxyl radical from a superoxide anion
radical and hydrogen peroxide requires the availability of at least one iron
coordination site that is either empty or occupied by a readily dissociable
ligand, such as water. This coordination with water may be completely
displaced by stronger ligands like azide (N3- ) anion. We have applied this
principle and determined free coordination site(s) (if any) in the Fe3+ (or
Cu2+)-antioxidant complex using a UV spectrophotometry method (Graf et
a/, 1984; Martell et a/, 1957). The results are recorded in Tablesl and 2.
Example 3 showed the absence of any water coordination (that is, the
complex is fully and firmly saturated and there is no room for any pro-
oxidant activity via the formation of oxo-ferryl or oxo-cupryl radical). All
other antioxidants/chelators showed disparate coordination site(s) thereby
allowed for the formation of oxo-ferryl or oxo-cupryl radicals and
manifesting a pro-oxidant effect, particularly at low concentrations. Example
3 a s t he m ost e ffective c helator o f I oose i ran and copper, would prevent
oxidative stress-induced damage to hair and skin caused by radicals and
loose transition metal ions. Two commercial cationic sunscreens, namely,
Escalol® HP 610 and Incroquat® UV 283 do not have iron-or copper-
Phase B. Mix until mixture is homogeneous and cool to about 50 C. Add
Phase C to the above mixture and stir well.
Adjust pH using citric acid to 5-6.
Example 7: Deep conditioner Formulation with vegetable protein
Heat Phase A to 70 - 75 C with agitation. In a separate vessel, heat Phase
B to 70 - 75 C until melted. Add B to A with agitation. Cool to 50 C add
Phase C and D with stirring. Allow to cool to room temperature. Then add
Phase E, if needed with stirring.
Heat Phase A to approximately to 75 C. Stir Phase B; heat to 75 C. Add B
to A with stirring. Homogenize and cool down the temperature to about 50
C and add Phase C.
Protection of Artificial Hair Color Fading (Auburn Color)
The UV photoprotection of hair is tested for compound of Example 3 in
comparison to a control formulation. The lightness and color changes over
time of UV-B irradiation of auburn-dyed hair were measured by using an X-
Rite L.a.b. instrument. L is lightness in color, a is color in red-green axis & b
is color in blue-yellow axis. Measured quantities are:
AE = [(Al)2+(Aa)2+(Ab)2]1'2
AC = [(Aa)2+(Ab)2]1'2
Two samples of hair were irradiated: one treated with base formulation
without active (Control) and the another one with active containing 2%
compound from Example 3.
Method of Product Application on to Hair
Apply, directly by hand, a pre-weighted amount of concentrated product on
a pre-weighted hair-strand. The amount of active ingredient per gram of
hair has been chosen as 50 mg. Hair strands were given 48 h to dry before
combing and exposure to UV B (2 MED/ hr).
Results are given in Figures 5 and 6
Effect after 36 hr UV-B exposure
62% reduction in AE vs control
54% reduction in AC vs control
Effect after 60 hr UV-B exposure
56% reduction in AE vs control
54% reduction in AC vs control
Similar studies were done as described in Example 10 using bleached and
colored hairs (other than auburn) with about 50% reduction in color fading.
Protection of DisulfideBond in Hair Protein Keratin
Protocol for Merbromin test for determining disulfide bond cleavage of hair
Three hair strands were tested by the procedure:
a- A non treated and non irradiated control strand,
b- a non treated but irradiated strand and
c- a treated and irradiated strand.
50 mg of active per gm applied on to auburn-dyed hair (hand application of
a 2% formulation). Hair strands were exposed to UV B irradiation for 60 h.
The Merbromin staining was done following the steps described below.
1. Preparation of an aqueous staining solution of 1% Merbromin
(Mercurochrome) and 0.5% Triton
2. Two hair strands, treated with a control formulation (without active)
and the active formulation, were exposed to UV B irradiation for 60 h at the
rate of 2 MED / h.
3. After photo-exposure, hair strands were immersed in the staining
solution for 1 h at room temperature. Then, they were thoroughly rinsed,
shampooed three times with 10% ALS solution, and soaked for 96 h in 1%
ALS solution with a daily solution change. The non-irradiated hair was
submitted to a double shampooing with 1% ALS solution. After the final
rinse, hair strands were dried at room temperature and measured by use of
a MA68 handheld colorimeter from X-Rite.
4. The L.a.b. values were measured and expressed in terms of total
color difference AE = (AL2+Aa2+Ab2)1/2 and a chromaticity difference AC =
(Aa2+Ab2)1/2 between unexposed and exposed hair strands (Figure 7).
The dying duration in mercurochrome was 1 h, followed by shampooed
washing and 96 h soaking in 1 % aqueous Laureth sulfate solution.
The preceding examples can be repeated with similar success by
substituting the generically or specifically described reactants and/or
operating conditions of this invention for those used in the examples.
From the foregoing description, one skilled in the art can easily ascertain
the essential characteristics of this invention, and without departing from
the spirit and scope thereof, can make various changes and modifications
of the invention to adapt it to various usages and conditions.
Reduction in Hair Color Fading During Repeated Shampooing
Auburn -dyed hair was shampooed 10 times with a 2% aqueous solutions
of SLS without and with 1% of compound according to example 3. Color
changes are quantified by L.a.b. measurements at different times of
shampooing (0, 5 and 10 shampoos).
Method: A 9 g swatch of hair is dipped and stirred for 2 minutes by hand in
a 200 ml test solution containing 2% SLS as to remain covered by foam.
They were then thoroughly rinsed under slightly warm water and dried at
room temperature for 2 h, followed by drying at 80F for an additional hour.
At the time of measurement, hair swatches were combed to align all hair
fibers parallel and L.a.b. values measured with a X-Rite colorimeter.
Results: Simple shampooing of hair swatches increases the L and b values
(Fig. 8), i.e. the hair becomes lighter and shifts toward yellow. If the
shampoo includes 1% compound according to example 3, no significant
change in L or b values are observed. However, a decrease in "a" value is
observed which is due to the compound according to example 3
accumulation over repeated shampooing. This is confirmed by separate
L.a.b. measurements of auburn hair swatches with different amounts of
compound according to example 3 applied as a conditioner (figure 9). The
a value clearly decreases proportionally with the concentration. This data
indicates that the product is substantive and can be delivered from
BRIEF DESCRIPTION OF THE|DRAWINGS
Figure 1 is a bar graph which illustrates the relative absorbance of UV-A
radiation over time by three UV absorbing compounds.
Figure 2 is a bar graph which illustrates the relative absorbance of UV-B
radiation over time by three UV absorbing compounds.
Figure 3 is graph of product uptake of a hair sample vs. time for two
Figure 4 is graph of product uptake of a hair sample vs. time for three
Figure 5: Protection oi Artificial Hair Color Fading expressed in terms of
total color difference AE (according to example 10).
Figure 6: Protection of Artificial Hair Color Fading expressed in terms of
chromaticity difference AC (according to example 10).
Figure 7: Protection of Disulfide Bond in Hair Protein Keratin expressed in
terms of total color difference AE and chromaticity difference AC (according
to example 12).
Figure 8: Reduction in Hair Color Fading During Repeated Shampooing
(L.a.b. values) according to example 13.
Figure 9: Induction of Hair Color Change During Repeated Shampooing
(L.a.b. values) according to example 13.
1. A compound of Formula 1
R is methoxy, or one R is H and other R is methoxy;
R1 is selected from the group consisting of COCH3, CO2R5, CONH2, CONH(R6)2,
CN, COX(CH2)n-N-(R2)(R3), and the quatemiztd salt form of the formula
X is 0 or NH;
n is an integer of 1 to 5;
Y is an anion;
R2, R3 and R4 are independently linear or branched C1 to C20 alkyl;
R5 and R6 are independently hydrogen or linear or branched C1-C20 alky I.
wherein R1 is selected from the group consisting of COCH3, CO2R5, CONH2,
C0NH(R6)2/ CN, COX(CH2)n-N-(R2)(R3), and the quaternized salt form of the
and wherein X is O or NH.
3. A compound as claimed in claim 1 or 2 wherein R1 is COCH3 or
4. A compound as claimed in one of claims 1 to 3 wherein X is 0.
5. A compound as claimed in one of claims 1 to 3 wherein X is NH.
6. A compound as claimed in one of claims 1 to 5 wherein the integer n is 2
7. A compound as claimed in claims 1 to 6 wherein the anion Y is
selected from C1, Br, alky) sulfate, alky) sulfonate, and p-tolylsulfonate, and
preferably is selected from alkyl sulfonate or alkyl sulfate.
8. A compound as claimed in claims 1 to 7 wherein R4 is independently
linear or branched C1 to C8.
9. A hair care formulation comprised of a compound or a mixture of at least
one of claims 1 to 8 alkyl.
10. A mixture comprised of at least one compound of at least one of claims
to 8 and at least one other sunscreen agent.
11. A mixture comprised of at least one compound of at least one of claims
to 8 and at least one additional sunscreen agent not of Formula 1, wherein
the compound of Formula 1 is capable of stabilizing at least one additional
sunscreen agent against photode gradation.
12. A cosmetic method of protecting a substrate from UV radiation which
comprises applying a compound of at least one of claims 1 to 8 to hair.
13. A method as claimed in claim 12 wherein the substrate protected from
UV radiation is selected from the group consisting of polymers, textile fabrics,
Leathers and paints.
14. A method of improving the photostability of a hair care formulation the
method comprising adding a compound of formula 1 of at least one of the
claims 1 to 8 to the formulation in an amount sufficient to.improve the
photostability of the formulation.
15. A method of improving the antioxidant activity of a hair care formulation
the method comprising adding a compound of formula 1 of at least one of
the claims 1 to 8 to the formulation in an amount sufficient to improve the
antioxidant activity of the formulation.
16. A method of improving the photostability of a composition consisting of
sunscreen agents not of Formula 1 of claim 1 said method comprising adding
a compound of formula 1 of at least one of the claims 1 to 8 to said
composition in an amount sufficient to improve the photostability of said
17. A method of improving the antioxidant activity of a composition
consisting of sunscreen agents not of Formula 1 of at least one of the claims
1 to 8 said method comprising adding a compound of formula 1 of at least
one of claims 1 to 8 to said composition in an amount sufficient to improve
the antioxidant activity of said composition.
18. An article comprised of at least one compound of at least one of the
claims 1 to 8 and a hairpiece.
19. An article comprised of at least one compound of at least one of the
claims 1 to 8 with a substrate selected from the group consisting of polymers,
textile fabrics, leathers and paints.
20. A compound as claimed in claim 1 of the following formula:
22 A hair care formulation comprised of a compound or a mixture of
compounds of at least one of the claims 1 to 8 capable of protecting
against UV-B or UV-A rays or against UV-A and UV-B rays.
A compound of Formula 1
wherein R is methoxy, or one R is H and other R is methoxy;
R1 is selected from the group consisting of COCH3, CO2R5,
CONH2,CONH(R6)2,CN,COX(CH2)n-N-(R2)(R3), and the quaternized salt form
of the formula COX(CH2)n-N-(R2)(R4)(R3)+; X is O or NH; n is an integer of 1
to 5; Y is an anion; R2, R3 and R4 are independently linear or branched C1 to
C20 alkyl; and R5 and R6 are independently hydrogen or linear or branched C1-
|Indian Patent Application Number||1656/KOLNP/2004|
|PG Journal Number||10/2009|
|Date of Filing||04-Nov-2004|
|Name of Patentee||MERCK PATENT GMBH|
|Applicant Address||FRANKFURTER STRASSE 250, 64293 DARMSTADT|
|PCT International Classification Number||C07C 235/80|
|PCT International Application Number||PCT/EP2003/03182|
|PCT International Filing date||2003-03-27|