Note: Descriptions are shown in the official language in which they were submitted.
~2~3'7~1~
25724-85
It is known that a series of organoleptically-active substances,
especially odorant substances, produce undesired ~i.e. phototoxic) reactions on
or in the skin when they are applied to the skin (e.g. as components of
cosmetic preparations) and are there-lpon exposed to the influence of light.
These reactions can be accompanied by subjective and objective phenomena of the
exposed skin such as itchillg, inflammations, swellings, reddenings, burnings.
The present invention is concerned with a method for the prevention
of such phototoxic reactions caused by odorant substances or odorant substance
compositions; the method comprises using for this purpose 4-(1,1-dimethylethyl)-
4'-methoxydibenzoylmethane, a substance which has been found to have a very good
tolerance both dermally and systemically.
The present invention therefore provides a method for the prevention
of phototoxic reactions caused by application to skin of an odorant substance
or of a composition containing an odorant substance, which method comprises
applying to the skin an amount of 4-(1,1-dimethylethyl)-4'-methoxydibenzoyl-
methane which is effective to prevent phototoxic reactions.
The invention is also concerned with odorant substances or odorant
substance compositions which contain 4-(1,1-dimethylethyl)-4'-methoxydiben-
zoylmethane.
The invention is also concerned with the use of 4-(1,1-dimethylethyl)-
4'-methoxydibenzoylmethane, also referred to hereinafter as l'dibenzoylmethane",
for the prevention of phototoxic reactions caused by odorant substances or
odorant substance compositions.
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The most important produc:ts which usually produce
phototoxic reactions are odorant substance ccmpositions of
natural origin, especially a series of citrus oils such as,
for example, bergamot oil, lemon oil, lime oil, orange oil
and grapefrult oil. However, angelica oil or cumin oil can
also be mentioned in this connection.
As synthetic, organoleptically-active substances
which usualLy produce phototoxic reactions there can be
mentioned, in particular, methyl N-methylanthranilate and
5-acetyl-1,1,2,3,3,6-hexamethylindane ("Phantolide").
The amount of dibenzoylmethane to be added con-
veniently lies in the r~nge of about o.l to about 5 weightpercent, preferably about 0.1 to about 2 weight percent,
of the product to be protected.
The dibenzoyLmethane can be added to the product
20 as such or dissolved in a solvent or solv~nt mixture (~Og.
in ethanol).
9795
The following Example illustrates the present
invention: '
Example
Determination of the phototoxic potential of
various products; guinea pigs were used as the experimental
animals.
The investigations were carried out under standard
conditioni. With the exception of the irradiation periods
the animals were kept permanently in wire cages at a
temperature of 22 + 2C and a relative atmospheric humidity
of 45 - 10%. The daylight cycle was 12 hours/day.
Diet: standard feed and fresh water ad llbitum.
Light source: W-Lamp Westinghouse FS 40 "Blac~
Lamp"; energy: 1 x 104 erg/cm2/sec., spectrum: 320-400
nm, irradiation dosage: 20 j/cm2.
The male and female guinea pigs used weighed
between 300-~So g.
Prior to the experimental periods it was ensured
that all experimental animals were healthy.
The testmaterial(with or withoutadded dibenzoylmethane)
wasapplied inthe highestpossible concentrationwhich was ini -
tiallynon-irritating to the skin.Alcohol, acetone,water, pe-
trolatum or other suitable solvents were used to dilute or susperd
the test material.In addition,2%of dimethylsulphoxide were
added to the solutions or incorporated into the preparation
in order to increase the skin Penetration.
The test preparations were used as such or option-
ally diluted.
~97~i
Dosage: For the experiments the ~lcoholic, aceto-
nic or aqueous solutions were applied to the skin in an
amount of 0.025 ml/cm by means of a pipette. In the case
of solutions in petrolatum or ir the case or preparations
such as creams, salves, lotions etc amounts of 0.01 ml/2
cm2 were applied~
Observation periods: Obser~ation and evaluation of
the skin reaction was carried out 4, 24 and 48 hours after
the application of the test material.
Experimental proceduxe: A group of 4 guinea pigs
was used to determine the tolerance threshold of the
individual test materials p~ior to the induction phase.
In order to determine the highest possible concentration,
the test material was applied to the flank (0.25 ml/2 cm2)
not only undiluted but also diluted or suspended in
suitable solvents in concentrations of 30%, 10%, 3~ and 1%
(or when necessary in even lower concentrations) and left
uncovered.
Ex~erimental phase (induction phase): Both flanks
of at least 10 guinea pigs were shaved a~ least 2 hours
prior to the application of the test material. Thereupon,
a maximum of 5 circles each of 2 cm2 were marked on each
flank. On 4 of these circular sites there was applied
0.025ml of alcoholic, acetonic or a~ueous test solution
(highest initially non-irritating concentration) or O.Cl ml
of test solution, which was applied using other solvents
or preparations such as creams, salves or lotions.
The fifth application site was in each case treated
with a 0.1% alcoholic solution of 8-methoxypsoralen and
served as the control.
~22979~
30 minutes after the application of the test
material the left flank of each experimental animal was
exposed to a non-erythema producing W-A irradiation
(20 j/cm2). The right fla~k remained non-irradiated aftex
the application of the test material and served as the
control.
Observation and evaluation: The animals were
investigated for erythema and oedema formation 4, 24 and 48
hours after the application of the test material. ~he
skin reaction was evaluated either with -, which signified
no reaction, or with +, which signified a positive re-
action.
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