Note: Descriptions are shown in the official language in which they were submitted.
lZ690~5
ANTIPERSPIRANT COMPOSITION
This invention relates to improving the antiperspirant
effectiveness of compositions comprising zirconyl hydroxy
S chloride and aluminum chlorhydroxide and to such impro~ed
compositions in solid stable form.
It has hitherto been proposed to increase the
antiperspirant effectiveness of aluminum chlorhydroxide by
aging under specified conditions an aqueous solution containing
the aluminum chlorhydroxide, as described in Gosling et al.
U.S. Patent 4,359,456 and in British Patent Application
_ publi~hed December 10, 1980
No. 2,048,229A/until the solution exhibits specified
characteristics. In the British application, it is pointed out
that the increased activity is the result of a group of
complexes called Al~ characterized by having a diffusion
constant in gel permeation chromatography which is within the
range generally found for the Alb group of complexes but
which displays a complexing rate in the ferron test which is in
the range of the Al' complexes and by having molecules which
are less than 100 A in size in aqueous solution. The Al'
complexes thus prepared are stable in aqueous solution at ~
concentrations in the range 10~ to 30~.
It has now been found that a composition comprising
zirconyl hydroxy chloride and aluminum chlorhydroxide, unlike
aluminum chlorhydroxide alone, does not form a stable aqueous
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solution when heated, but that a different molecular complex
displaying increased antiperspirant effectiveness is formed by
heating an aqueous solution containing at least the aluminum
chlorhydroxide component and mixing with it the zirconium
hydroxy chloride component. The zirconium hydroxy chloride may
be present initially or can be added at any time during or
after heating. The novel complex, of lower molecular weight
than Al' , contains no zirconium, and reverts rapidly in
aqueous solution at room temperature to one containing less of
the novel complex, losing approximately 1/2 of its initial
concentration in 48 hours. The composition containing the
novel complex as described herein displays improved
antiperspirant efficacy as compared to an aqueous solution made
j by dissolving conventional zirconyl hydroxy chloride and
aluminum chlorhydroxide in water or as compared to conventional
commercially available aqueous solutions containing the
zirconyl and aluminum compounds. ~he novel complex can be
formed at least in part from the higher molecular weight Al'
complex of the prior art and is segregated in a separate zone
from Al'' when the aqueous solution is subjected to gel
' ~ permeation chromatography. When the aqueous solution
i
containing both aluminum chlorhydroxide and zirconyl hydroxy
chloride is subjected to heating, the Al' complex initially
present in the solution gradually decreases in amount while at
the same time the amount of the novel complex present gradually
increases. An aqueous solution containing the novel complex of
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the present inventio~ in large amount is unstable at room
temperature, as stated above, and the amount of the novel
complex present in such a solution decreases quite rapidly
while the amount of Al' increases. Because of this inherent
instability, aqueous solutions of zirconyl hydroxy chloride and
aluminum chlorhydroxide containing the novel complex of the
present invention cannot be used as such as a commercially
practical antiperspirant. However, it has been found that if
the a~leous solution containing the novel complex is rapidly
solidified by removal of water, the soiid product retains in
large part the desired complex and its high antiperspirant
effectiveness. The solid product consequently can be employed
as an antiperspirant in finely-divided form, e.g. in a powder
either alone or with a diluent powder vehicle such as talc, or
in the form of a cream or suspension in a non-aqueous liquid
vehicle, for example a high viscosity cream for manual
application, a low viscosity suspension for roll-on
application, or a suspension in a liquefied propellant for
aerosol application. Any conventional non-aqueous
physiologically and cosmetically acceptable non-toxic vehicle
can be used with the particulate solid composition of the
present invention to form an antiperspirant composition.
; Particle size may vary over a wide range out preferably is from
- l to lO0 micrometers in diameter. Relative proportions of
vehicle and particulate solid are not critical. In general,
the weight of particulate solid may range from 0.1 to 80% or
more of the total weight of the composition including vehicle.
0~
After the finely-di~ided solid comes into contact with the
skin, it dissolves in the initial perspiration present on the
skin and becomes effective as an antiperpirant.
The present invention comprises a stable solid
composition comprising zirconyl hydroxy chloride and aluminum
chlorhydroxide in which the atomic ratio of Al to Zr is from
6:1 to 1:1 having high antiperspirant efficacy, said
composition, when dissolved in water to form a 10% by weight
solution and, after storage at room temperature for no more
than 2 hours, subjected to gel permeation chromatography on
cross-linked dextran having a molecular weight exclusion range
of 1000 to 30,000 for globular proteins (Sephadex G-50),
exhibits a distribution pattern having peaks at Kd=0.7 and
Kd=0.5 in which the ratio of the height of the first peak to
that of the second is at least 1.5:1.
All of the chromatograms referred to herein are
obtained by passing aqueous solutions at 10~ concentration
through the specified cross-linked dextran column, employing as
eluent 0.1 molar aqueous KCl adjusted to pH3 with HCl, and
monitoring the refractive index of the eluent.
The invention also comprises the method of making an
antiperspiran~ composition having high efficacy which comprises
providing a 2% to 18% solution of aluminum chlorhydroxide in
water, heating the solution at a temperature of at least sOC,
mixing zirconyl hydroxy chloride with the solution before,
during or after said heating step, the amount of said zirconyl
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compound being sufficient to provide an atomic ratio of Al:Zr
from 6:1 to 1:1, said heating being continued until measurement
by gel permeation chromatography of said solution at a
concentration of 10% on cross-linked dextran having a molecular
S weight exclusion range of looo to 30,000 for globular proteins
shows peaks at Rd=0.7 and Rd=0.5 and the ratio of the first
peak to the second is at least 2:1, and at least 80%,
preferably at least 90%, of the total aluminum is present
within said peaks, and subjecting said solution to rapid drying
to solid form, said solid, when dissolved in water to form a
10% by weight solution and, after storage at room temperature
for no more than two hours, subjected to gel permeation
chromatography on said cross-linked dextran exhibiting a
distribution pattern having peaks at Rd=0.7 and at Rd=0.5 in
lS which the ratio of the height of the first peak to that of the
second peak is at least 1.5:1, preferbly at least 2:1. The
; amount of zirconyl hydroxy chloride added is such that the
. mixed solution contains 2 to 20% by weight of total solids; the
zirconyl hydroxy chloride may be mixed with the solution after
drying has begun and before viscosity has increased to the
point where mixing is difficult and must be mixed with it
before the solution has been completely dried. ~he zirconyl
hydroxy chloride can be in solid form or in aqueous solution
when mixed with the aluminum chlorhydroxide; when mixed with
the solution after drying has begun, the zirconium hydroxy
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chloride is preferably introduced in the form o an aqueous
solution, preferably at a concentration of 30~ to 55%: it may
contain an amino acid such as glycine. The mixing may be
carried out at room temperature or at elevated temperatures up
to the maximum temperature at which the heating is conducted.
Although heating of the aluminum chlorhydroxide solution, with
or without the addition of the zirconyl hydroxy chloride, is
required to produce the desired new complex in substantial
amount, once the necessary heating has been completed without
addition of the zirconyl compound the desired complex forms
very rapidly after the introduction of the zirconyl compound.
The invention also comprises the method of increasing the
antiperspirant eficacy of a composition comprising zirconyl
hydroxy chloride and aluminum chlorhydroxide which comprises
providing a 2~ to 20% solution in water of such composition in
which the atomic ratio of Al to Zr is from 6:1 to l:l, heating
the solution at a temperature of at least 50C until the ratio
of the height of a peak at Kd=0~.7 to that of a peak at Kd=0.5
as measured by gel permeation chromatography of a lO~ aqueous
solution on cross-linked dextran having a molecular weight
`! exclusion range of lO00 to 30,000 for globular proteins is at
least 2:1, then subjecting the solution to rapid drying to
solid form, said solid, when dissolved in water to form a 10%
by weight solution and subjected to gel permeation
chromatography on said cross-linked dextran after storage at
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room temperature for no more than 2 hours, exhibiting a
distribution pattern having peaks at Kd=0.7 and at Kd=0.5 in
which the ratio of the height of the first to that of the
second peak is at least 1.5:1, preferably at least 2:1.
In the appended drawings,
Fig. 1 represents a chromatogram of a freshly prepared
10% by weight aqueous solution of zirconyl hydro~ chloride and
aluminum chlorhydroxide;
Fig. 2 represents a chromatogram of the solution of
Fig. 1 after heating at 100C for 2 hours; peak 4 is at Kd=0.7
and peak 3 is at Rd=0.5; .
Fig. 3 is a plot s~lowing the ratio of the heights of
peak 4 (Rd=0.7) to peak 3 ~Kd=0.5) of chromatograms of a 10%
aqueous solution of the aluminum and zirconium compounds heated
for varying time periods at 50OC;
Fig. 4 is a plot showing the ratio of the heights of
peak 4 (Kd=0.7) to peak 3 (Kd=0.5) of chromatograms of the
- splution of Fig. 1 when heate~ a,t reflux for varying time
, periods;
Fig. 5 is a plot showing the ratio of heights of
peak 4 (Rd=0.7) to peak 3 (Kd=0.5) during room temperature ~.
storage of the aluminum and zirconium compounds after I-
previously heating at 100C for 46 hours;
, Fig.. 6a shows the chromatogram of a 10% aqueous
solution of a mixture of zirconium and aluminum compounds of
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the present invention after heating at 100C fo,r 20 hours; peak
4 is at Kd=0.7 and peak 3 is at Kd=0.5;
Fiq. 6b is a chromatogram of a 10% aqueous solution of
the solid made by spray-drying the solution of Fig. 6a; peaks 4
and 3 are as stated in Fig. 6a;
Fig. 7a is a chromatogram of a 10~ aqueous solution of
the zirconium and aluminum compounds of the present invention
after heating at 100C for 17 hours; peak 4 is at Kd=0.7 and
peak 3 is at Kd=0.5;
Fig. 7b is a chromatogram of a 10% aqueous solution of
the solid product made by freeze-drying the solution of Fig.
7a; peaks 4 and 3 are as stated in Fig. 7a;
The compositions of zirconyl hydroxy chloride and
aluminum chlorhydroxide which can be employed in the present
invention include those in which the zirconyl compound has the
formula ZrO(OH)~Cly where X+Y=2 or a hydrate thereof and
the aluminum compound has the formula Al 2 (OH), nCln where
n is from 0.8 to 2 or a hydra~e ~hereof, n preferably being 1.
The atomic proportion of aluminum to zirconium in the
composition may vary from about 1:1 to 6:1. The atomic
proportion of metal to chloride may vary from about 0.9 to,
1.9. The inclusion in the composition of a neutral amino acid
as described in Grad U.S. Patent 2,854,382,
does not have an adverse
effect upon the formation of the desired novel complex.
Commercially available compositions of zirconyl hydroxy
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1~690'~S
chloride and aluminum chlorhydroxide mixtures frequently
contain glycine as the neutral amino acid in an amount such
that the molar ratio of glycine to zirconyl hydroxy chloride is
about 1:1. The glycine or other neutral amino acid aids in
preventing gelation of the aqueous solution before or during
the heating step of the method of the present invention; and
its presence does not prevent formation of the desired complex
and does not interfere with the conversion of the heated
solution to solid orm nor with the subsequent use of the solid
as an antiperspirant. Solid compositions as well as aqueous
solutions containing zirconyl hydroxy chloride an!d aluminum
chlorhydroxide are available commercially, usually containing a
water solution amino acid to prevent gelling; these materials
may be employed in practicing the present invention. The
individual zirconyl and aluminum components can also be
~' obtained co~mercially and mixed in solution.
It is preferred for best results to make the
,1,
composition by employing as starting material an aqueous
solution containing aluminum chlorhydroxide at a concentration
of 8~ to 153 by weight (all concentrations hereinafter are by
weight) to which is added after the desired heating aD amount
of zirconyl hydroxy chloride containing an approximately
;~ eguimolar quantity of glycine, the amount of zirconyl compound
~, being sufficient to provide an atomic ratio of Al to Zr equal
to about 4:1. It is essential that the solution containing the
; desired complex be dried rapidly to solid form; preferably, the
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12~i90~5
zirconium compound is added to the solution after drying has
begun but before the solution becomes so concentrated that
mixing is difficult: for example, the finely divided solid
zirconium hydroxy chloride monoglycinate can 'oe mixed with the
solution when it has been partially dried to a concentration of
45%-55~ by thin film vacuum flash evaporation, a~d after
dissolution is complete drying can be completed by spray drying
to solid form. The extent of heating of the aluminum
chlorhydroxide solution before addition of the zirconyl
compound is optional, but in the preferred embodiment it is
heated at a temperature of at ~east 50C, preferably 70 to
100, to the extent that no further hea'ing after addition of
the zirconyl compound (except for whatever heat is needed for
drying) is required to form the desired complex. Although
temperatures above 100C can be used, pressure vessels are
needed for higher temperatures adding to the expense, so that
temperatures from 70C to 100C are most preferred. When the
heating is carried out at 80~C~using a 10% aqueous solution,
approximately 16 hours heating is required. If the heating of
the aluminum chlorhydroxide solution is insufficient to achieve
the specified condition before the zirconyl hydroxy chloride is
mixed with it, the solution containing both the aluminum and
the zirconyl compound can be heated to achieve the desired
result.
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In the case where there has been no heating of the
aluminum chlorhydroxide solution before adding the zirconyl
compound to it, the complex of the invention can be made by
providing an aqueous solution containing a mixture of zirconyl
S hydroxy chloride and aluminum chlorhydroxide in an amount from
about 2% to about 20% by weight of the total solution,
preferably 8 to 15%, and heating it at a temperature of at
least 50C, preferably 70C or hiqher. After heating has
been continued for several hours an aliquot sample of the
solution is subjected to gel permeation chromatography on a
cross-linked dextran, (Sephadex G-50) using as the eluent 0.1
molar aqueous KCl with the pH adjusted to 3.0 with HCl; and the
distribution of the metal complexes is measured by monitoring
the refractive index of the eluent. As appears from Fig. 1, 6
peaks occur in the case of a typical freshly prepared 10% by
weight aqueous solution containing zirconyl hydroxy chloride
and aluminum chlorhydroxide (Al) 2 (OH) sCl . Peak 1 as shown
in the drawing is the eluent fraction containing the zirconium
compound; this compound is excluded by the gel because of its
large molecular size. Peak 2 contains the Al' complex, and
peak 3, at Kd=0.5 contains the Al' complex. Peak 4 at
Kd=0.7, which appears only as a shoulder between peaks 3 and 5
contains the hitherto unrecognized novel complex which is
present only in small proportion, while peaks 5 and 6 are
~ractions containing Al' or other lower molecular weight
compounds.
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As appears from Fig. 2 of the drawing, the solution
characterized in Fig. 1, after heating at 100C for 2 hours,
displays a quite different distribution of complexes when
subjected to gel permeation chromatography under the same
conditions, the most striking change being a large decrease in
the height of peak 3 at Kd=0.5 and a very large increase in the
height of peak 4 at Kd=0.7. It has been found that the extent
of antiperspirant efficacy of the composition is generally
proportional to the relative heights of peak 4 and peak 3, i.e.
to the relative amounts of the complex of peak 4 at Kd=0.7
present in the composition as compared to the Al' complex of
peak 3 at Rd=0.5. Those compositions in which the ratio of the
height of peak 4 to that of peak 3 is at least 1.5:1,
preferably at least 2:1 display the desired superior
antiperspirant efficacy.
The length of time of heating necessary to achieve the
desired ratio of height of peak 4 at Kd=0.7 to peak 3 at Kd=0.5
depends upon the temperature an~d the concentration of the
solution. The higher the temperature, the more rapid is the
increase in ratio. To achieve a ratio of height of peak 4 to
peak 3 of 3 or more, it is necessary to heat solutions of a
concentration of 2-10% at a temperature of 80C or more.
In the case of a 10% aqueous solution heated at 50OC,
as shown in Fig. 3 of the drawing, the ratio of the height of
peak 4 at Kd=0.7 to that of peak 3 at Kd=O.S rapidly approaches
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a maximum and thereafter remains substantially constant as
heating is continued, This is typical of the results obtained
at other temperatures and concentrations, as can be seen from
Fig. 4 of the drawing which shows the chanse in the ratio of
S peak 4 to peak 3 of a 10% aqueous solution when heated at
reflux temperature.
The rate of reversion at room temperature of a 10%
aqueous solution which had previously been heated at 100C for
46 hours is shown in Fig. 5 of the drawing, from which it is
clear that the ratio of reversion is so rapid that it is not
commercially practical to package for sale aqueous solutions
having a hiqh ratio of peak 4 at Kd=0.7 to peak 3 at Kd=0.5.
The following specific examples are intended to
illustrate more fully the nature of the present invention
without acting as a limitation upon its scope.
Example 1
Approximately 1 liter of an aqueous solution
containing (10% solids) ZrO(OH)~Cl, Al2(0H)sCl and glycine
in which the atomic ratio of Al to Zr was 3.6 to 1 and the
ratio of Zr to glycine was 1:1 was heated at 100C for 20 hours.
A portion of the solution, within less than 2 hours
after coolinq to room temperature, was subjected to gel
permeation chromatography on a cross-linXed dextran
(Sephadex G-50) column using pH 3, 0.lM KCl as the eluent, and
the refractive index of the eluent fractions was measured. The
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resulting chromatogram is shown in Fig. 6a. It exhibits
successive peaks in which the height of peak 4 at Kd=0.7 is
several times the height of pedak 3 at Kd=0.5, similar to that
of Fig. 2.
S Another portion of this heated solution was
immediately subjected to spray-drying on a Buchi model 190
spray drier with an inlet temperature of 147C and an outlet
temperature of 80C to provide a fine, dry powder.
A portion of the powder was then redissolved in water
to form a 10% by weight solution and within less than 2 hours
was subjected to gel permeatioP chromatography under the same
conditions as the earlier solution. The resultant chromatogram
is shown in Fig. 6b of the drawir,g, from which it is clear that
the ratio of the height of peak 4 at Kd=0.7 to that of peak 3
lS at Kd=O.S was not greatly changed.
Example 2
A different specimen of a 10% aqueous solution of the
same mixture of zirconyl, alumi~num and glycine compounds was
aged 17 hours at 100C; its gel permeation chromatographic
characteristics, measured as in Example 1, are shown in Fig. 7a
of the drawing. A specimen of the aged solution was
immediately subjected to freeze-drying using a Virtis Unitrap
Freeze-Drier. The dried residue was ground and passed through
a 200 mesh sieve.
A portion of the powder was then redissolved in water
to form a 10% by weight solution and subjected to gel
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permeation chromatography under the same conditions as the
earlier solution. The resultant chromatogram is shown in
- Fig. 7b of the drawing. The slight reduction in ratio of
height of peak 4 at Kd=0.7 to that of peak 3 at Kd=0.5 after
5 freeze-drying while somewhat greater than the reduction which
occurred in the case of spray-drying, still produced a product
having enhanced antiperspirant activity as compared to the
antiperspirant activity of the original aqueous solution
characteri~ed in Fig. 1 of the drawing.
~oth the spray-dried and the freeze-dried solid
powders exhibited no further substantial change in
chromatographic characteristics during storage at room
temperature for several months.
Typical antiperspirant formulations in which the
15 material of the present invention may be practically employed
are as follows:
I. Non-aqueous Roll-On
; Weiqht %
Finely divided solid of
present invention 20.0
Quaternium-18 Hectorite 2.7
Anhydrous Alcohol SDA-40 1.6
~2 0.2
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lZ690~5
Cyclomethicone, a
silicone oil 75.5
Perfume q-5
II. Stick AntipersPirant
Weiqht
Finely divided solid of
present invention 23.0
Ozokerite Wax 22.4
Myristyl Alcohol 17.2
Cyclomethicone 17.9
PPG-15 Stearyl ether 11.5
Steareth-15 2.3
Bentone Gel IPM 5.7
-~ Perfume q.s
III. Aerosol AntipersPirant
Finely divided solid of
present invention 7.0
Talc 2.0
Anhydrous Alcohol SDA-40 4.2
Quaternium-18 Hectorite 1.4
Cyclomethicone 4.0
Isopropyl myristate 3.0
Perfume 0.1
Propellant-A31 78.3
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The product of the present invention has been
evaluated for antiperspirant activity using standard Hot Room
clinical testing procedures both as a 10% aqueous solution, and
as a dry powder in a non-aqueous roll-on formulation. In each
case, it was found to be superior to the analogous conventional
material having the gel permeation characteristics as shown in
Fig. 1 of the drawing.
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