Note: Descriptions are shown in the official language in which they were submitted.
CA 02240684 1998-06-15
1
DESCRIPTION
AEROSOL PREPARATION
Technical Field
The present invention relates to an aerosol
preparation which when sprayed forms a sherbet-like
solid on the sprayed site and has an enhanced cooling
effect.
B~ck~round Art
It is effective to cool the affected part in
order to quickly calm the pain caused by contusion,
sprain, muscular fatigue, etc. or the itch caused by
1 5 ath I ete' s foot, i nsect b i te, etc. I n the past, the
aerosol preparations which when sprayed do not form a
sherbet-like solid have been used frequently for such
symptoms. However, since such aerosol preparations do
not have a durable cooling effect on the skin, a durable
calming effect of pain or itch on the affected part
cannot be achieved by these aerosol preparations. The
specifications of W090/11068 and Japanese Patent Kokai
4-103526 disclose aerosol preparations which form a
sherbet-like foam gel for solving such drawbacks.
However, such prior art aerosol preparations require
complicated procedures such as heating and emulsifying
procedures for the production of the concentrate, and
have a problem of low efficacy in the production.
In addition, it is essential to contain water
in the known~aerosol preparations which when sprayed
form a sherbet-like solid, because the durable cooling
effect of these preparations can be obtained by freezing
water which is contained therein. Accordingly, it is
impossible to contain drugs labile in water or highly
lipophilic drugs in the known preparations.
CA 02240684 1998-06-15
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Disclosure of the Invention
As a result of extensive research in order to
solve the above-mentioned purposes, the present inven-
tors have found that an aerosol preparation comprising a
lower alcohol, a higher alcohol and a liquefied gas does
not require an emulsifying procedure for the production
and has a durable cooling effect because the aerosol
preparation forms a sherbet-like solid when sprayed, and
whereby the present invention has been accomplished.
That is, the present invention relates to an
aerosol preparation which when sprayed forms a sherbet-
like solid, which comprises a concentrate containing a
lower alcohol having 1 to 3 carbon atoms and a higher
alcohol having at least 12 carbon atoms, and a propel-
lant containing a liquefied gas.
Any known aerosol preparations form a solid,
when sprayed, by freezing water which is contained
therein, on the contrary, the aerosol preparation of the
present invention does not always necessarily contain
water, and it is characterized by that the aerosol
preparation forms a solid under entirely new conditions
when sprayed.
According to the aerosol preparation of the
present invention, the higher alcohol which is cooled by
the heat of vaporization of the liquefied gas including
the lower alcohol forms a sherbet-like solid when spray-
ed.
In the present invention, the lower alcohol
having 1 to 3 carbon atoms means a straight or branched
alcohol, for~example, methanol, ethanol, denatured etha-
no I , propano I , i sopropano I , etc. , and preferab I y etha-
nol. The amount of the lower alcohol is preferably 0.3
to 65 96 by weight based on the total amount of the
preparat i on, more preferab I y 1 . 5 to 50 96 by we i ght and
most preferably 15 to 35 96 by weight. If the amount of
the I ower a I coho I i s I ess than 0. 3 96 by we i ght, the
CA 02240684 1998-06-15
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concentrate cannot be easily mixed with the propellant
homogeneously. If the amount of the lower alcohol is
more than 65 96 by weight, since the amount of the pro-
pellant is relatively reduced, the cold feeling is
reduced.
The higher alcohol having at least 12 carbon
atoms of the present invention means a straight or
branched alcohol which can be homogeneously mixed with
other components, for example, lauryl alcohol, cetanoi,
stearyl alcohol, cetostearyl alcohol, behenyl alcohol,
lanolin alcohol, hydrogenated lanolin alcohol, etc, they
may be used alone or by mixture with each other, and
stearyl alcohol or cetanol is preferable.
The amount of the higher alcohol is preferably
1 5 0. 005 to 14 96 by we i ght based on the tota I amount of the
preparat i on, more preferab I y 0. 015 to 10 96 by we i ght and
most preferably 0.5 to 5 ~ by weight. If the amount of
the h i gher a t coho I i s I ess than 0. 005 96 by we i ght, s i nce
the aerosol preparation cannot easily form the solid
when sprayed, the durable cold feeling is reduced. On
the other hand, if the amount of the higher alcohol is
more than 14 96 by weight, since the higher alcohol
cannot be easily dissolved, the production procedure is
complicated.
The higher alcohol must be absolutely dis-
solved in the lower alcohol and the liquefied gas so as
to give a homogeneous system, and whereby the effect of
the present invention can be achieved. For the purpose,
when the higher alcohol cannot be sufficiently dis-
solved, it i's possible to contain other solvents or
so I ub i I i z i ng agents (e. g. po I yoxyethy I ene a I ky I ether,
polyoxyethylene hydrogenated caster oil, diisopropyl
az i pate, i sopropy I myr i state, 1 , 3-buty I eneg I yco I ,
propyleneglycol, polyethyleneglycol, glycerin, lactic
ac i d, sod i um hydrox i de, etc. ) .
The liquefied gas is any one which can be used
CA 02240684 1998-06-15
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as a propellant for an ordinary aerosol preparation, but
preferably dimethyl ether, n-butane, i-butane, propane
or a liquefied petroleum gas, and they can be used alone
or by mixture with each other. The amount of the lique-
fled gas is preferably 30 to 95 96 by weight based on the
total amount of the preparation, and more preferably 50
to 85 9o by weight. If the amount of the liquefied gas
is less than 30 96 by weight, the cold feeling by the
aerosol preparation is reduced, and whereby the calming
effect of pain and itch is reduced. On the other hand,
if the amount of the liquefied gas is more than 95 9b by
weight, the aerosol preparation does not form a sherbet-
like solid when sprayed, and therefore the durable
cooling effect cannot be easily obtained.
When the conditions for which the aerosol
preparation of the present invention forms a sherbet-
like solid are distinguished between the concentrate and
the propellant of the aerosol preparation, it is neces-
sary to contain at least 6 96 by weight of the lower
alcohol having 1 to 3 carbon atoms in the concentrate,
at least 1 96 by weight of the higher alcohol having at
least 12 carbon atoms in the concentrate and 0.5 to 20
parts by weight of the liquefied gas based on 1 part by
weight of the concentrate.
The aerosol preparation of the present inven-
tion can be prepared by dissolving the lower alcohol and
the higher alcohol to give a homogeneous system, and if
desired, adding such other components that do not de-
stroy the homogeneous system, and filling the resulting
concentrate .together with the liquefied gas into an
aerosol container. Examples of the aerosol container
include containers made of metals or plastics as used
usually. fn view of the durable cooling effect, it is
preferable to contain a suitable amount of water as such
another component that does not destroy the homogeneous
system. In case of addition of water to the concen
CA 02240684 1998-06-15
trate, not more than 90 96 by we i ght of water can be
added based on the total amount of the concentrate, but
preferably 20 to 60 9o by weight of water is added to the
concentrate in view of easy preparation design.
In order to enhance the~calming effect on pain
and itch on the affected part, the aerosol preparation
of the present invention can contain such drug-effective
ingredients that do not degrade the effect of the pres-
ent invention, for example, anti-inflammatory and anal-
ges i c agents (e. g. i ndomethac i n, meths 1 sa I i cy I ate,
monoglycol salicylate, ketoprofen, flurbiprofen, piroxi-
cam, d i c I ofenac, i buprofen, mephenam i c ac i d, dexametha-
sone acetate, etc. ) , ant i prur i t i cs (e. g. crotam i ton,
i chthammo I , mochthamo I , thymo I ac i d, etc. ) , ant i funga I
1 5 agents (e. g. amoro I f i n hydroch I or i de, undecy I en i c ac i d,
pentachlorophenol, clotrimazole, tolnaftate, tricho-
mycin, miconazole nitrate, lanoconazole, sulconazole
n i trate, oxyconazo I a n i trate, b i fonazo I e, etc. ) , ant i -
histaminic agents (e. g. diphenhydramine, diphenhydramine
hydrochloride, isothipendyl hydrochloride, etc.). local
anesthet i cs (e. g. I i doca i ne, d i buca i ne hydroch f or i de,
etc. ) , ant i b i of i cs (e. g. potass i um i od i de, ch I orohex i -
d i ne g I uconate, acr i no I , benza I kon i um ch I or i de, etc. ) ,
antiphlogistics (e. g. penicillin, tetracycline hydro-
chloride, fradiomycin, kanamycin, etc.), refrigerants
(e. g. 1-mentho I , camphor, mentha o i I , etc. ) , and the
like. The amounts of these drug-effective components
are d i fferent i nd i v i dua I I y, but preferab I y 0. 001 to 10 96
by weight based on the total amount of the preparation.
Th.e aerosol preparation of the present inven-
tion can contain, if necessary, any additives usable for
ordinary aerosol preparations as long as they do not
degrade the effect of the present invention, for exam-
p I e, ant i-ox i dants (e. g. d i buts I hydroxyto I uene, etc. ) ,
percutaneous absorption promoters (e. g. glycerin esters
of fatty acid, fats, aliphatic carboxylates, nicoti
CA 02240684 1998-06-15
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nates, azone, alkyleneglycol esters of fatty acid,
etc. ) , perfumes, dyes and the I i ke.
Industrial Utilizabilitv
The present invention makes it possible to
provide an aerosol preparation which when sprayed forms
a sherbet-like solid, does not require a complicated
emulsifying procedure for the production, and has a
cooling effect comparable to that of the prior art
products.
Best Mode for Carryina Out the Invention
The present invention is illustrated in more
detail by the following examples and test example.
Examale 1
4.76 parts by weight of stearyl alcohol and
28.53 parts by weight of ethanol were mixed, stirred and
dissolved homogeneously to give a concentrate. The con-
centrate was filled into a pressure-resistant container,
and a valve was attached to the container, into which
0.07 part by weight of propane, 1.93 parts by weight of
n-butane, 0. 93 pa rt by we i ght of i -butane and 63. 78
parts by weight of dimethyl ether were then filled. A
spout for spraying was attached to the container to give
an aerosol preparation.
- Examale 2
0. 31 pa rt by we i ght of i ndomethac i n, 4. 1 1
parts by weight of diisopropyl azipate, 1.23 parts by
weight of polyoxyethylene alkyl ether, 16.47 parts by
weight of denatured ethanol, 13.39 parts by weight of
purified water and 1.23 parts by weight of cetanol were
mixed, stirred and dissolved homogeneously to give a
concentrate. The concentrate was filled into a pres-
sure-resistant container, and a valve was attached to
the container, into which 63.26 parts by weight of
dimethyl ether was then filled. A spout for spraying
CA 02240684 1998-06-15
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was attached to the container to give an aerosol prepa-
rat i on.
Examale 3
0.35 part by weight of miconazole nitrate,
1.76 parts by weight of diisopropyl azipate, 1.05 parts
by weight of isopropyl myristate, 0.70 part by weight of
glycerin, 15.80 parts by weight of denatured ethanol and
8. 74 parts by we i ght of pur i f i ed water, 0. 53 part by
weight of stearyl alcohol, 0.53 part by weight of cetano
I, 0.70 part by weight of polyoxyethylene alkyl ether
and 0.35 part by weight of polyoxyethylene hydrogenated
caster oil were mixed, stirred and dissolved homoge-
neously to give a concentrate. The concentrate was
filled into a pressure-resistant container, and a valve
was attached to the container, into which 69.49 parts by
weight of dimethyl ether was then filled. A spout for
spraying was attached to the container to give an aero-
sol preparation.
~om_parative Example 1
Following the same method as in Example 1
using the formulation of Example 1 in which stearyl
alcohol was replaced with ethanol, there was obtained an
aerosol preparation.
Comc~arative Examcle 2
Following the same method as in Example 2
using the formulation of Example 2 in which polyoxy-
ethylene alkyl ether and cetanol were replaced with
denatured ethanol and purified water respectively, there
was obtained an aerosol preparation for comparison.
ComAarative Examale 3
0.36 part by weight of miconazole nitrate,
1 . 79 parts by we i ght of d i i sopropy I az i pate, 1 . 07 parts
by weight of isopropyl myristate, 0.71 part by weight of
glycerin, 17.06 parts by weight of denatured ethanol and
8.27 parts by weight of purified water were mixed,
stirred and dissolved homogeneously to give a concen-
CA 02240684 1998-06-15
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trate. The concentrate was filled into a pressure-
resistant container, and a valve was attached to the
container, into which 70.74 parts by weight of dimethyl
ether was then filled. A spout for spraying was at-
tached to the container to give an aerosol preparation
for compar i son.
Comaarative Example 4 (An_aerosol preparation which re-
quires an emulsifying procedure
for the production)
1 0 0. 31 part by we i ght of i ndomethac i n, 4. 07
parts by weight of diisopropyl azipate, 1.22 parts by
weight of polyoxyethylene sorbitan monostearate, 0.81
part by weight of polyoxyethylene sorbitan tristearate
and 1.22 parts by weight of sorbitan monostearate were
dissolved with heating, and mixed thoroughly with 15.94
parts by weight of hot purified water. After cooling
with stirring, the mixture was mixed with 14.23 parts by
weight of denatured ethanol and dispersed homogeneously
to give a concentrate. The concentrate was filled into
a pressure-resistant container, and a valve was attached
to the container, into which 62.20 parts by weight of
dimethyl ether was then filled. A spout for spraying
was attached to the container to give an aerosol prepa-
rat i on.
Test Example 1
A thermocouple sensor was fixed on a peace of
sheet with adhesive tapes, and the sheet was spread on a
thermostat water bath controlled at 33°C. The aerosol
preparations obtained in Examples 1 to 3 and Comparative
Examples 1 to 4 were each sprayed on the thermocouple
sensar for 3 seconds. Properties of the aerosol prepa-
ration were confirmed when sprayed, and the values shown
by the thermocouple sensor with time were measured.
Results are shown in Table 1.
CA 02240684 1998-06-15
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CA 02240684 1998-06-15
The aerosol preparations of Examples 1 to 3
and Comparative Example 4 formed a sherbet-like solid
when sprayed, but those of Comparative Examples 1 to 3
did nat form any sherbet-like solid. In the change of
5 temperature on the thermocouple sensor, the temperatures
by the aerosol preparations of Comparative Examples 1 to
3 were at least 30°C at 30 seconds after the spray and
returned to the original temperature at 45 seconds after
the spray, on the contrary, the aerosol preparations of
10 Examples 1 to 3 and Comparative Example 4 were found to
have a durable cooling effect.
