U.S. patent application number 11/103284 was filed with the patent office on 2005-09-01 for anti-microbial antiperspirant products.
This patent application is currently assigned to UNILEVER HOME & PERSONAL CARE USA, DIVISION OF CONOPCO, INC.. Invention is credited to Landa, Andrew Sjaak, Makin, Stephen Anthony, McKay, Victoria Anne.
Application Number | 20050191255 11/103284 |
Document ID | / |
Family ID | 26243425 |
Filed Date | 2005-09-01 |
United States Patent
Application |
20050191255 |
Kind Code |
A1 |
Landa, Andrew Sjaak ; et
al. |
September 1, 2005 |
Anti-microbial antiperspirant products
Abstract
Anti-microbial products comprising an antiperspirant active and
an amount of transition metal chelator sufficient to enhance the
deodorancy performance of said antiperspirant active, are claimed.
The transition metal chelator salt improves the anti-microbial
performance of the antiperspirant active and the two components can
be co-formulated. Particular products are antiperspirant deodorant
compositions. Preferred chelator salts have high affinity for iron
(III).
Inventors: |
Landa, Andrew Sjaak;
(Wirral, GB) ; Makin, Stephen Anthony; (Wirral,
GB) ; McKay, Victoria Anne; (Wirral, GB) |
Correspondence
Address: |
UNILEVER INTELLECTUAL PROPERTY GROUP
700 SYLVAN AVENUE,
BLDG C2 SOUTH
ENGLEWOOD CLIFFS
NJ
07632-3100
US
|
Assignee: |
UNILEVER HOME & PERSONAL CARE
USA, DIVISION OF CONOPCO, INC.
|
Family ID: |
26243425 |
Appl. No.: |
11/103284 |
Filed: |
April 11, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11103284 |
Apr 11, 2005 |
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09764829 |
Jan 17, 2001 |
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6893630 |
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Current U.S.
Class: |
424/65 |
Current CPC
Class: |
A61K 8/046 20130101;
A61K 8/26 20130101; A61K 8/44 20130101; A61K 8/347 20130101; A61K
8/28 20130101; A61Q 17/005 20130101; A61K 8/84 20130101; A61Q 15/00
20130101; A61K 2800/51 20130101; A61K 8/34 20130101 |
Class at
Publication: |
424/065 |
International
Class: |
A61K 007/32 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 18, 2000 |
GB |
0001131.2 |
Jan 18, 2000 |
GB |
0001130.4 |
Claims
1. An antimicrobial-product comprising an antiperspirant active and
a transition metal chelator that is a micro-molar active
anti-microbial agent, wherein the ratio of the transition metal
chelator to the anti-perspirant active is from 1:3 to 1:50 by
weight.
2. (canceled)
3. An anti-microbial product according to claim 1 wherein the ratio
of the transition metal chelator to the antiperspirant active is
from 1:5 to 1:25 by weight.
4. An anti-microbial product according to claim 1, comprising a
liquid or soft solid composition.
5. An antimicrobial product according to claim 4, having a hardness
such that the pressure required to penetrate the composition is
less than 0.06 N.mm.sup.-2.
6. An anti-microbial product according to claim 1, comprising an
aerosol composition.
7. An anti-microbial product according to claim 1, wherein the
antiperspirant active is an aluminium, zirconium, or mixed
aluminium/zirconium salt.
8. An anti-microbial product according to claim 6, wherein an
aluminium halohydrate is a component of the aerosol
composition.
9. (canceled)
10. (canceled)
11. (canceled)
12. An anti-microbial product according to claim 1, wherein the
transition metal chelator has an acid form comprising at least five
acid groups.
13. An anti-microbial product according to claim 1, wherein the
transition metal chelator is a polyaminocarboxylic acid or salt
thereof.
14. An anti-microbial product according to claim 13, wherein the
transition metal chelator is diethylenetriaminepentaacetic acid or
a salt thereof.
15. An anti-microbial product according to claim 1, comprising an
additional organic anti-microbial agent.
16. An anti-microbial product according to claim 15, comprising a
polyhexamethylene biguanide salt, triclosan, or farnesol.
17. An anti-microbial product according to claim 1, comprising
fragrance material at up to 4% by weight of the composition.
18. (canceled)
19. A cosmetic method of reducing perspiration and providing
additional control of bacterial numbers on a human body surface,
said method comprising the topical application to the human body of
a product according to claim 1.
20. A cosmetic method according to claim 19, resulting in reduced
body odour.
21. (canceled)
22. A method for the manufacture of an anti-microbial composition
comprising the mixing of an antiperspirant active, a transition
metal chelator, and a carrier fluid, wherein the transition metal
chelator comprises a chelator capable of reducing the growth of
Staphylococcus epidermidis by at least 30%, pursuant to the
procedure set forth in the instant specification under the heading
"Anti-microbial Performance of Chelators".
23. An anti-microbial product according to claim 1 wherein the
transition metal chelator comprises
ethylenebis[2-(2-hydroxyphenyl)glycine] (EDDHA) or a salt
thereof.
24. An anti-microbial product according to claim 21 wherein the
transition metal chelator comprises a chelator with phosphonic acid
groups, or a salt thereof.
25. An anti-microbial product comprising (a) an antiperspirant
active, (b) a transition metal chelator having a binding
coefficient for iron (III) of greater than 10.sup.10, and (c) an
additional anti-microbial agent comprising polyhexamethylene
biguanide salt, triclosan, or farnesol.
26. An anti-microbial product according to claim 25 wherein the
transition metal chelator has a binding coefficient for iron (III)
of greater than 10.sup.26.
27. An anti-microbial product according to claim 1 wherein the
transition metal chelator comprises a chelator capable of reducing
the growth of Staphylococcus epidermidis by at least 30%, pursuant
to the procedure set forth in the instant specification under the
heading "Anti-microbial Performance of Chelators".
Description
FIELD OF INVENTION
[0001] This invention relates to the field of anti-microbial
compositions and to methods of reducing microbial numbers. In
particular, this invention is concerned with reducing microbial
numbers upon the surface of the human body and thereby reducing
body odour. The compositions and methods involved utilise a
transition metal chelator together with an antiperspirant active.
When used on the human body, the compositions and methods of the
invention are of greatest benefit when used on the most malodorous
areas of the body, for example the underarm areas or feet.
BACKGROUND
[0002] Typically, a deodorising composition will attempt to
significantly reduce or prevent body odour by reducing either
perspiration or the number of viable micro-organisms on the body
surface as represented herein by skin. The former is usually
referred to as an antiperspirant composition and the latter a
deodorant. Other compositions attempt to mask body malodours using
perfumes.
[0003] Compositions reducing perspiration often comprise a metal
salt, such as an aluminium or zirconium salt, which blocks the
sweat pores. This method is very simple and has proven to be
beneficial, yet perspiration is rarely reduced by more than
50%.
[0004] Deodorants, on the other hand, reduce the numbers of viable
micro-organisms on the surface of the skin. It is well known that
sweat is usually odourless until it has been degraded by the skin
microflora. Typical deodorants include ethanol and triclosan
(2',4,4'-trichloro, 2-hydroxy-diphenyl ether) which is a well known
anti-microbial agent. However, the deodorising effect obtained with
such deodorants wears off with the passage of time and the
microflora progressively recover their numbers.
[0005] There is, therefore, a continuing requirement for effective
and long lasting antiperspirant deodorant compositions for the
market. The problem to be solved is not simply reducing sweating
and initial microbial numbers on the body surface; equally
important is maintaining low microbial numbers (particularly low
bacterial numbers) on the body surface (particularly in the most
malodorous areas, eg. the axilla).
[0006] Transition metal chelators have previously been incorporated
into antiperspirant deodorant compositions as formulation aids.
U.S. Pat. No. 5,516,511 (Procter and Gamble Co.) discloses
particular antiperspirant gel compositions in which chelators are
used during manufacture to prevent reaction between the active and
the primary gellant, the latter component comprising
12-hydroxystearic acid or a derivative thereof. U.S. Pat. No.
5,849,276 (Procter and Gamble Co.) mentions chelators in
antiperspirant stick compositions, although such materials are
stated to be optional "non-active" components. The gellants
exemplified in this patent are again 12-hydroxystearic acid and
derivatives thereof, and also N-lauroyl-glutamic acid dibutyl amide
and 2-dodecyl-N.N'-dibutyl-succinam- ide.
[0007] Transition metal chelators have also been disclosed in
simple deodorant compositions, that is to say, deodorant
compositions excluding antiperspirant actives. U.S. Pat. No.
4,356,190 (Personal Products Co.) discloses the use of selected
aminopolycarboxylic acid compounds for inhibiting malodour
formation; WO 97/01360 (Concat Ltd.) claims a method of inhibiting
bacterial growth using particular substituted polyaza compounds
that show affinity for first transition series elements; WO
97/44006 (Ciba Speciality Chemicals Holding, Inc.) claims the use
of nitrogen-containing complexing agents for the anti-microbial
treatment of the skin and of textile fibre materials; and WO
97/02010 discloses the use of chelators selected from the succinic
acid, glutaric acid, and phosphonic acid classes as bactericidal
compounds.
[0008] Other patents indicate that transition metal chelators can
improve the efficacy of specific known anti-microbials. WO 98/12399
(Public Health Research Institute of the City of New York)
discloses improved performance of lanthionine-containing
bacteriocins in compositions also comprising a transition metal
chelator. WO 97/09974 (Laboratoire Medix) discloses compositions
comprising chlorhexidine and a chelator. EP 0019670 B1 (Glyco
Chemicals, Inc.) discloses anti-microbial compositions comprising a
condensation product of 5,5-dimethyl hydantoin and formaldehyde in
combination with a water-soluble chelating agent selected from
ethylenediaminetetraacetic acid (EDTA),
diethylenetriaminepentaaceti- c acid (DTPA) or the alkali metal
salts thereof. U.S. Pat. No. 4,199,602 (Economics Laboratory, Inc.)
discloses the potentiation of anti-microbial nitroalkanes by
aminocarboxylic-type chelating agents. U.S. Pat. No. 5,688,516
(University of Texas System et al) discloses compositions
comprising non-glycopeptide anti-microbials (other than vancomycin)
in combination with a selection of components, including a
chelating agent. WO 99/10017 (University of Texas System et al)
discloses a method for controlling the growth of micro-organisms
using a chelating agent and an anti-microbial agent. GB 1,420,946
(Beecham Group Ltd.) discloses that the activity of selected
phenolic anti-microbials can be vastly increased by certain
chelating agents, in particular the disodium salt of EDTA.
SUMMARY OF THE INVENTION
[0009] It has been discovered that the combined use of an
antiperspirant active and an effective amount of a transition metal
chelator gives surprisingly good and long-lasting anti-microbial
benefits. When such treatment is applied to the human body, highly
effective malodour control results. An important function of the
antiperspirant active is to reduce initial microbial numbers on the
surface being treated, whilst the transition metal chelator
functions to augment the maintenance of low microbial numbers.
Surprisingly, it has been found that the two components can be used
together without detrimental interactions affecting either the
performance of the components or the stability of compositions
containing both the components. On application to the human body,
additional hygiene and malodour control derive from the
antiperspirancy benefit also delivered.
[0010] According to a first aspect of the present invention, there
is provided an anti-microbial product comprising an antiperspirant
active and an amount of transition metal chelator sufficient to
enhance the deodorancy performance of said antiperspirant
active.
[0011] According to a second aspect of the present invention, there
is provided a method of controlling microbial numbers comprising
the application to a substrate of a product comprising an
antiperspirant active and an amount of transition metal chelator
sufficient to enhance the deodorancy performance of said
antiperspirant active. A particular application of this aspect of
the invention is the control of microbial numbers on the surface of
the human body, for example skin, and the resulting control of body
odour. This particular application also provides a method for
reducing perspiration and providing additional control of bacterial
numbers on the body surface, eg. skin surface. This method may also
be used to deliver enhanced fragrance intensity from a
fragrance-containing product according to the invention.
[0012] According to a third aspect of the present invention, there
is provided a method for the manufacture of an anti-microbial
composition comprising the mixing of an antiperspirant active, a
transition metal chelator, and a carrier fluid.
DETAILED DESCRIPTION
[0013] The antiperspirant active and the transition metal chelator
both function as effective anti-microbial agents in this invention.
On application to the human body, the reduced perspiration benefit
delivered by the antiperspirant active is also beneficial and
further contributes to the deodorancy benefit resulting from the
anti-microbial performance of the components of the product.
Without wishing to be bound by theory, it is hypothesised that
after reduction of microbial numbers by the antiperspirant active,
the transition metal chelator effectively inhibits the up-take of
essential transition metal ion nutrients by the remaining microbes,
thereby minimising their re-growth. Surprisingly, there is no
detrimental interaction between the antiperspirant active and the
transition metal chelator and an excellent anti-microbial and
deodorancy performance is obtained from the products of the
invention.
[0014] It is not essential that the antiperspirant active and the
chelator are part of the same composition. The anti-microbial
benefit derived from use of the invention may be gained by
independent application of the antiperspirant active and the
chelator. Such application may be concurrent or consecutive,
provided that the treated substrate experiences the presence of
both components at the same time. When the components are applied
from independent compositions, it is preferred that the product
also comprises a means for, and/or instruction for, both of the
compositions to be applied to the substrate requiring
treatment.
[0015] It is preferred that the anti-microbial product of the
invention comprises an antiperspirant active and a transition metal
chelator that are both present in the same composition. The
benefits found with such compositions can include good product
aesthetics, lack of product separation, attainment of the desired
rheology, visco-stability, good dispensing, and any combination of
these benefits or others.
[0016] The method of controlling microbial numbers offered by the
invention is particularly useful because the benefit can extend for
many hours, for example 5 hours, or 24 hours, or even longer, after
application of the product to the substrate. When the substrate is
the skin of the human body, this can result in an extended
deodorancy benefit; that is to say, extended inhibition of
generation of human body odour.
[0017] The antiperspirant active and the chelator may be present in
the composition or compositions of the invention in any form. For
example, either or both of the agents may be used neat or may be
diluted with a volatile propellant and used as an aerosol; with an
additional liquid and used, for example, as a roll-on or
squeeze-spray product; or with a thickener or structurant and used,
for example, as a cream, gel or solid stick product.
[0018] The anti-microbial product of the invention may be applied
to the substrate requiring treatment by any means. Frequently, the
substrate requiring treatment is a surface. Application of liquid
compositions can be by absorption onto a carrier matrix like paper,
fabric, or sponge and application by contacting said carrier matrix
with the surface. Solid or semi-solid compositions can be applied
by direct contact or can be dissolved or dispersed in a liquid
medium prior to application. Application can also comprise a
combination of any two or more of the above techniques.
Chelators
[0019] Preferred transition metal chelators have affinity for iron
(III), preferably high affinity for iron (III); that is to say, a
binding constant for iron (III) of greater than 10.sup.10, or, for
optimum performance, greater than 10.sup.26. The `iron (III)
binding constant` referred to above is the absolute stability
constant for the chelator-iron (III) complex. Such values are
independent of pH and are measured on the most anionic, fully
deprotonated form of the chelator. Measurements can be made
potentiometrically, and in a number of other ways. Full details of
suitable methods can be found in "Determination and Use of
Stability Constants", A. E. Martell and R. J. Motekaitis (VCH, New
York, 1989). Tables of applicable values may be found in numerous
sources, for example "Critical Stability Constants", R. M. Smith
and A. E. Martell (Plenum Pub. Corp., 1977).
[0020] Preferred chelators are "micro-molar active"; that is to
say, they are able to significantly inhibit the growth of a
relevant micro-organism when present, in a medium containing said
micro-organism, at a concentration of 3.times.10.sup.-6
mol.dm.sup.-3 or less. Inhibition is considered significant when
growth of the relevant micro-organism on a supporting medium can be
reduced by at least 30%, preferably by at least 45%. When the
surface to be treated is human skin, a relevant micro-organism is
Staphlococcus epidermidis and chelators capable of achieving
significant inhibition include diethylenetriaminepentaacetic acid
(DTPA) and triethylenetetraaminehexaacetic acid (TTHA), but exclude
ethylenediaminetetraacetic acid (EDTA) and
trans-1,2-diaminocyclohexane-N- ,N,N',N'-tetraacetic acid
(CDTA).
[0021] The chelator may be used in its acid form, but it may also
be used as one of its salts.
[0022] The iron (III) chelators used in the present invention
preferably have acid forms with at least two, more preferably at
least four, and most preferably at least five, ionisable acid
groups. The acid groups are preferably carboxylic and/or
phosphonic, but may be sulphonic or phosphinic, or any mixture of
these groups.
[0023] Preferred chelators with phosphonic acid groups are, in the
acid form, diethylenetriaminepenta(methylphosphonic) acid (DTPMP),
ethanehydroxydiphosphonic acid (EHDP),
ethylenediaminetetra(methylenephos- phonic acid) (EDTMP), and
hexamethylenediaminetetra(methylenephosphonic acid) (HMDTMP).
[0024] Particularly suitable chelators for use include
polycarboxylate compounds, in particular aminopolycarboxylate
compounds. The acid forms of the aminopolycarboxylate compounds
include EDTA, CDTA, ethylenediaminedisuccinic acid (EDDS). More
preferred aminopolycarboxylate chelators have the acid forms DTPA,
TTHA, and ethylenebis[2-(2-hydroxyphenyl)glycine] (EDDHA).
[0025] The chelators or salts thereof preferably have only moderate
molecular weight, by which it is meant that the chelators, in their
acid forms, have a molecular weight of less than 1000, more
preferably 200 to 800, and most preferably 290 to 580, and in their
salt form have a molecular weight of less than 2000, more
preferably 300 to 1400, and most preferably 500, to 1000.
[0026] The chelator is preferably incorporated into a composition
at a level of 0.01% to 10%, more preferably at a level of 0.05% to
5%, and most preferably at a level 0.3% to 3% by weight of the
non-volatile components of the composition. Mixtures of chelator
salts may also be used. In aerosol compositions comprising greater
than 50% by weight of volatile propellant a preferred level of
chelator may be 0.5% to 8% by weight of the non-volatile components
of the composition.
[0027] Herein, non-volatile components are those having a boiling
point greater than 20.degree. C. at atmospheric pressure.
[0028] As already mentioned, the chelator may be used in its acid
form or as one of its salts. Preferred salts, for certain
applications, are monovalent alkali metal salts such as sodium and
potassium salts. For certain other applications, for example
formulation in alcohol-based compositions, salts with organic
counter-ions are preferred, for example protonated or quaternised
amines. Salts formed using aliphatic amines are generally preferred
to those formed from aromatic amines. A further preference is for
protonated or quaternised amine cations possessing a
C.sub.1-C.sub.10 terminal hydrocarbyl group, wherein a hydrocarbyl
group is a radical comprising solely carbon and hydrogen atoms.
Such relatively hydrophobic organic counter-ions lead to
particularly good compatibility between the chelator salt and the
organic anti-microbial.
[0029] Preferred protonated or quaternised amine cations of the
chelator salts are of formula
R.sup.1R.sup.2R.sup.3R.sup.4N.sup.(+), wherein R.sup.1 is H or
CH.sub.3; R.sup.2, R.sup.3, and R.sup.4 are each independently H or
an aliphatic or aromatic substituent containing 0 to 3 hydroxyl
groups, optionally interrupted and/or substituted by functional
groups such as ether, amine, ester, or amide; with the provisos
that at least one of R.sup.2, R.sup.3, or R.sup.4 comprises a
C.sub.1-C.sub.10 terminal hydrocarbyl group, optionally R.sup.2 and
R.sup.3 together forming a ring as the terminal hydrocarbyl group,
and that R.sup.2, R.sup.3, and R.sup.4 are not all
CH.sub.2CH(OH)CH.sub.3 groups.
[0030] Particularly preferred chelator-amine salts are salts of
2-amino-2-methyl-1-propanol, cyclohexylamine, diisopropanolamine,
or 2-amino-1-butanol.
[0031] Partial salts of chelator acids possessing more than one
acidic group may also be employed; such salts retain one or more
non-ionised acid groups. Also claimed are salts where the cations
are in part protonated or quaternised amines and in part some other
cation, for example an alkali metal cation, in particular a sodium
ion.
Antiperspirant Actives
[0032] Antiperspirant actives are preferably incorporated into a
composition in an amount of from 0.5-60%, particularly from 5 to
30% or 40% and especially from 5 or 10% to 30 or 35% of the weight
of the composition. The ratio of chelator and/or salt thereof to
antiperspirant active is preferably from 1:3 to 1:50 and more
preferably from 1:5 to 1:25 by weight.
[0033] Antiperspirant actives for use herein are often selected
from astringent active salts, including in particular aluminium,
zirconium and mixed aluminium/zirconium salts, including both
inorganic salts, salts with organic anions and complexes. Preferred
astringent salts include aluminium, zirconium and
aluminium/zirconium halides and halohydrate salts, such as
chlorohydrates.
[0034] Aluminium halohydrates are usually defined by the general
formula Al.sub.2(OH).sub.xQ.sub.y.wH.sub.20 in which Q represents
chlorine, bromine or iodine, x is variable from 2 to 5 and x+y=6
while wH.sub.2O represents a variable amount of hydration.
Especially effective aluminium halohydrate salts, known as
activated aluminium chlorohydrates, are described in EP 006,739
(Unilever PLC and NV). Some activated salts do not retain their
enhanced activity in the presence of water but are useful in
substantially anhydrous formulations, i.e. formulations that do not
contain a distinct aqueous phase. Aluminium halohydrates as
described herein are particularly preferred in aerosol
compositions.
[0035] Zirconium actives can usually be represented by the
empirical general formula: ZrO(OH).sub.2n-nzB.sub.z.wH.sub.2O in
which z is a variable in the range of from 0.9 to 2.0 so that the
value 2n-nz is zero or positive, n is the valency of B, and B is
selected from the group consisting of chloride, other halide,
sulphamate, sulphate and mixtures thereof. Possible hydration to a
variable extent is represented by wH20. Preferable is that B
represents chloride and the variable z lies in the range from 1.5
to 1.87. In practice, such zirconium salts are usually not employed
by themselves, but as a component of a combined aluminium and
zirconium-based antiperspirant.
[0036] The above aluminium and zirconium salts may have coordinated
and/or bound water in various quantities and/or may be present as
polymeric species, mixtures or complexes. In particular, zirconium
hydroxy salts often represent a range of salts having various
amounts of the hydroxy group. Zirconium aluminium chlorohydrate may
be particularly preferred.
[0037] Antiperspirant complexes based on the above-mentioned
astringent aluminium and/or zirconium salts can be employed. The
complex often employs a compound with a carboxylate group, and
advantageously this is an amino acid. Examples of suitable amino
acids include dl-tryptophan, dl-.beta.-phenylalanine, dl-valine,
dl-methionine and .beta.-alanine, and preferably glycine which has
the formula CH.sub.3CH(NH.sub.2)COOH.
[0038] It is highly desirable to employ complexes of a combination
of aluminium halohydrates and zirconium chlorohydrates together
with amino acids such as glycine, which are disclosed in U.S. Pat.
No. 3,792,068 (Procter and Gamble Co.). Certain of those Al/Zr
complexes are commonly called ZAG in the literature. ZAG actives
generally contain aluminium, zirconium and chloride with an Al/Zr
ratio in a range from 2 to 10, especially 2 to 6, an Al/Cl ratio
from 2.1 to 0.9 and a variable amount of glycine. Actives of this
preferred type are available from Westwood, from Summit and from
Reheis.
[0039] Other actives that may be utilised include astringent
titanium salts, for example those described in GB 2,299,506.
[0040] The proportion of solid antiperspirant salt in a composition
normally includes the weight of any water of hydration and any
complexing agent that may also be present in the solid active.
However, when the active salt is in solution, its weight excludes
any water present.
[0041] If the composition is in the form of an emulsion the
antiperspirant active will be dissolved in the disperse phase. In
this case, the antiperspirant active will often provide from 3 to
60% by weight of the aqueous disperse phase, particularly from 10%
or 20% up to 55% or 60% of that phase.
[0042] Alternatively, the composition may take the form of a
suspension in which antiperspirant active in particulate form is
suspended in the water-immiscible liquid carrier. Such a
composition will probably not have any separate aqueous phase
present and may conveniently be referred to as "substantially
anhydrous" although it should be understood that some water may be
present bound to the antiperspirant active or as a small amount of
solute within the water-immiscible liquid phase. In such
compositions, the particle size of the antiperspirant salts often
falls within the range of 0.1 to 200 .mu.m with a mean particle
size often from 3 to 20 .mu.m. Both larger and smaller mean
particle sizes can also be contemplated such as from 20 to 50 .mu.m
or 0.1 to 3 .mu.m.
Additional Components
[0043] An additional component that can sometimes augment the
efficacy of the composition is a further organic anti-microbial
agent. Most of the classes of agents commonly used in the art can
be incorporated into compositions of the invention. Levels of
incorporation are preferably from 0.01% to 3%, more preferably from
0.03% to 0.5%. Preferred organic anti-microbial agents have a
minimum inhibitory concentration (MIC) of 1 mg.ml.sup.-1 or less,
particluarly 200 .mu.g.ml.sup.-1 or less, and especially 100
.mu.g.ml.sup.-1 or less. The MIC of an anti-microbial agent is the
minimum concentration of the agent required to significantly
inhibit microbial growth. Inhibition is considered "significant" if
an 80% or greater reduction in the growth of an inoculum of a
relevant micro-organism is observed, relative to a control medium
without an anti-microbial agent, over a period of 16 to 24 hours at
37.degree. C. The "relevant micro-organism" used for testing should
be representative of those associated with the substrate to be
treated. When the substrate to be treated is human skin, a relevant
micro-organism is Staphylococcus epidermidis. Other relevant
micro-organisms include Coryneform spp., Salmonella spp.,
Escherichia Coli, and Pseudomonas spp., in particular P.
aeruginosa. Details of suitable methods for determining MICs can be
found in "Antimicrobial Agents and Susceptibility Testing", C.
Thornsberry, (in "Manual of Clinical Microbiology", 5.sup.th
Edition, Ed. A. Balows et al, American Society for Microbiology,
Washington D.C., 1991). A particularly suitable method is the
Macrobroth Dilution Method as described in Chapter 110 of above
publication (pp. 1101-1111) by D. F. Sahm and J. A. Washington II.
MICs of anti-microbials suitable for inclusion in the compositions
of the invention are triclosan: 0.01-10 .mu.g.ml.sup.-1 (J. Regos
et al., Dermatologica (1979), 158:. 72-79) and farnesol: ca. 25
.mu.g.ml.sup.-1 (K. Sawano, T. Sato, and R. Hattori, Proceedings of
the 17.sup.th IFSCC International Conference, Yokahama (1992) p.
210-232). By contrast ethanol and similar alkanols have MICs of
greater than 1 mg.ml.sup.-1. Preferred organic anti-microbials are
bactericides, for example quaternary ammonium compounds, like
cetyltrimethylammonium salts; chlorhexidine and salts thereof; and
diglycerol monocaprate, diglycerol monolaurate, glycerol
monolaurate, and similar materials, as described in "Deodorant
Ingredients", S. A. Makin and M. R. Lowry, in "Antiperspirants and
Deodorants", Ed. K. Laden (1999, Marcel Dekker, New York). More
preferred anti-microbials for use in the compositions of the
invention are polyhexamethylene biguanide salts (also known as
polyaminopropyl biguanide salts), an example being Cosmocil CQ.TM.
available from Zeneca PLC, preferably used at up to 1% and more
preferably at 0.03% to 0.3% by weight; 2',4,4'-trichloro,
2-hydroxy-diphenyl ether (triclosan), preferably used at up to 1%
by weight of the composition and more preferably at 0.05-0.3%; and
3,7,11-trimethyldodeca-2,6,10-trienol (farnesol), preferably used
at up to 1% by weight of the composition and more preferably at up
to 0.5%.
[0044] A carrier fluid is a highly desirable additional component
of many of the compositions of the invention. Such materials act as
solvents or carriers for the other components of the composition,
facilitating their delivery. Water can be used as a carrier fluid,
although it is more preferable to use mixtures of water and an
alcohol, especially ethanol. Alcohol/water mixtures are
particularly suitable carrier fluids in roll-on and pump spray
products. Cyclomethicones and other volatile silicones are another
class of carrier fluid that may be employed. Examples of this
latter class are Dow Corning silicone fluids 344, 345, 244, 245,
246, 556, and the 200 series; Union Carbide Corp. silicones 2707
and 7158; and General Electric silicone SF1202. Alternatively,
non-silicone hydrophobic liquids may be employed, such as mineral
oils, hydrogenated polyisobutene, polydecene, paraffins,
isoparaffins of at least 10 carbon atoms, and aliphatic and
aromatic ester iols. Propylene glycol, butylene glycol, and related
glycols may also be used. Other alternative carrier fluids include
materials having multiple functions, for example isopropyl
myristate, isopropyl palmitate, dipropylene glycol, and glycerol.
Mixtures of carrier fluids may also be employed to advantage.
Compositions preferably comprise carrier fluid at a level of from
30% to 98% by weight, or more preferably from 60% to 97% by weight,
of the non-volatile components of the composition.
[0045] Structurants and emulsifiers are further additional
components of the compositions of the invention that are highly
desirable in certain product forms. Structurants, when employed,
are preferably present at from 1% to 30% by weight of the
composition, whilst emulsifiers are preferably present at from 0.1%
to 10% by weight of the composition. In roll-ons, such materials
help control the rate at which product is dispensed by the roll
ball. In stick compositions, such materials can form gels or solids
from solutions or suspensions of the chelator salt in a carrier
fluid. Suitable structurants for use in such compositions of the
invention include cellulosic thickeners such as hydroxy propyl
cellulose and hydroxy ethyl cellulose, and dibenzylidene sorbitol.
Emulsion pump sprays, roll-ons, creams, and gel compositions
according to the invention can be formed using a range of oils,
waxes, and emulsifiers. Suitable emulsifiers include steareth-2,
steareth-20, steareth-21, ceteareth-20, glyceryl stearate, cetyl
alcohol, cetearyl alcohol, PEG-20 stearate, and dimethicone
copolyol. Suspension aerosols, roll-ons, sticks, and creams require
structurants to slow sedimentation (in fluid compositions) and to
give the desired product consistency to non-fluid compositions.
Suitable structurants include sodium stearate, stearyl alcohol,
cetyl alcohol, hydrogenated castor oil, synthetic waxes, paraffin
waxes, hydroxystearic acid, dibutyl lauroyl glutamide, alkyl
silicone waxes, quaternium-18 bentonite, quaternium-18 hectorite,
silica, and propylene carbonate. Some of the above materials also
function as suspending agents in certain compositions.
[0046] Further emulsifiers desirable in certain compositions of the
invention are perfume solubilisers and wash-off agents. Examples of
the former include PEG-hydrogenated castor oil, available from BASF
in the Cremaphor RH and CO ranges, preferably present at up to 1.5%
by weight, more preferably 0.3 to 0.7% by weight. Examples of the
latter include poly(oxyethylene) ethers.
[0047] Certain sensory modifiers are further desirable components
in the compositions of the invention. Such materials are preferably
used at a level of up to 20% by weight of the composition.
Emollients, humectants, volatile oils, non-volatile oils, and
particulate solids which impart lubricity are all suitable classes
of sensory modifiers. Examples of such materials include
cyclomethicone, dimethicone, dimethiconol, isopropyl myristate,
isopropyl palmitate, talc, finely-divided silica (eg. Aerosil 200),
particulate polyethylene (eg. Acumist B18), polysaccharides, corn
starch, C12-C15 alcohol benzoate, PPG-3 myristyl ether, octyl
dodecanol, C7-C14 isoparaffins, di-isopropyl adipate, isosorbide
laurate, PPG-14 butyl ether, glycerol, hydrogenated polyisobutene,
polydecene, titanium dioxide, phenyl trimethicone, dioctyl adipate,
and hexamethyl disiloxane.
[0048] Fragrance is also a desirable additional component in the
compositions of the invention. Suitable materials include
conventional perfumes, such as perfume oils and also include
so-called deo-perfumes, as described in EP 545,556 and other
publications. Levels of incorporation are preferably up to 4% by
weight, particularly from 0.1% to 2% by weight, and especially from
0.7% to 1.7% by weight.
[0049] It should be noted that certain components of compositions
perform more than one function. Such components are particularly
preferred additional ingredients, their use often saving both money
and formulation space. Examples of such components include ethanol,
isopropyl myristate, and the many components that can act as both
structurants and sensory modifiers, for example silica.
[0050] Further additional components that may also be included are
colourants and preservatives at a conventional concentration, for
example C.sub.1-C.sub.3 alkyl parabens.
Product Forms
[0051] The compositions of the invention may take any form.
Examples include wax-based sticks, soap-based sticks, compressed
powder sticks,. roll-on suspensions or solutions, emulsions, gels,
creams, squeeze sprays, pump sprays, and aerosols. Each product
form contains its own selection of additional components, some
essential and some optional. The types of components typical for
each of the above product forms may be incorporated in the
corresponding compositions of the invention.
[0052] Particular embodiments of the invention are anti-microbial
products comprising an antiperspirant active and an amount of
transition metal chelator sufficient to enhance the deodorancy
performance of said antiperspirant active, that are not gel-solid
stick compositions gelled by 12-hydroxystearic acid, esters of
12-hydroxystearic acid, amides of 12-hydroxystearic acid,
N-lauroyl-glutamic acid dibutyl amide, and
2-dodecyl-N,N'-dibutyl-succinamide.
[0053] Embodiments of the invention of this type include liquid and
soft solid compositions. The former compositions may be defined by
their ability to flow, whilst the latter compositions may be
defined by their lack of hardness, having a hardness less than the
lesser of 75 grams of force, as measured by the technique described
in U.S. Pat. No. 5,516,511 (Procter and Gamble), or 500 grams of
force, as measured by the technique described in U.S. Pat. No.
5,849,276 (Procter and Gamble). Hence, particular embodiments of
the invention comprise liquid and soft solid compositions having a
hardness such that the pressure required to penetrate the
composition is less than 0.06 N.mm.sup.-2.
[0054] The various product forms of the invention each have
additional components that are desirably present. Roll-on
compositions of the invention preferably have a low level of
non-volatile emollient present, for example isopropyl myristate or
propylene glycol at 0.2-2% by weight. Antiperspirant sticks have
cyclomethicone as the most preferred carrier fluid. Also preferably
present are one or more ethers or esters previously mentioned as
sensory modifiers; these materials can serve to mask deposits.
Wash-off agents are also desirable in such compositions.
Aerosol Compositions
[0055] Aerosol compositions of the invention are a particularly
preferred product form. Preferably the propellant is the major
component in such compositions, comprising from 30 to 99 parts by
weight, more preferably from 50 to 95 parts by weight.
[0056] The propellant is normally selected from liquified
hydrocarbons or halogenated hydrocarbon gases (particularly
fluorinated hydrocarbons such as 1,1-difluoroethane and/or
1-trifluoro-2-fluoroethane) that have a boiling point of below
10.degree. C. and especially those with a boiling point below
0.degree. C. It is especially preferred to employ liquified
hydrocarbon gases, and especially C.sub.3 to C.sub.6 hydrocarbons,
including propane, isopropane, butane, isobutane, pentane and
isopentane and mixtures of two or more thereof. Preferred
propellants are isobutane, isobutane/isopropane, isobutane/propane
and mixtures of isopropane, isobutane and butane.
[0057] Other propellants that can be contemplated include alkyl
ethers, such as dimethyl ether or compressed non-reactive gasses
such air, nitrogen or carbon dioxide.
[0058] The base composition, which is mixed with the propellant,
may comprise any of the following components as preferred
additional ingredients: a carrier fluid, a fragrance, an emollient
(eg. isopropyl myristate or propylene glycol) or an anticlogging
agent (in order to prevent or minimise the occurrence of solid
occlusions in the spray nozzle). Further components may be added to
mask powdery deposits, for example non-volatile oils, long chain
alcohols (eg. octyl dodecanol), ethers (eg. PPG-14 butyl ether), or
dimethicone fluids.
[0059] The aerosol composition is usually filled into an aerosol
canister that is capable of withstanding pressures generated by the
formulation, employing conventional filling apparatus and
conditions. The canister can conveniently be a metal canister
commercially available fitted with a dip tube, valve and spray
nozzle through which the formulation is dispensed.
Methods of Manufacture
[0060] The details of the relevant methods of manufacture depend
upon the product form concerned. The basic method comprises the
mixing of an antiperspirant active, a transition metal chelator,
and usually a carrier fluid. Other components are optionally added,
according to the form of composition desired.
EXAMPLES
[0061] (Note that"letter" codes refer to Comparative Examples.)
Preparation of Aerosol Antiperspirant Deodorants
[0062] Example 1 (see Table 1B) was prepared in the following
manner. 0.54 g of quaternium-18-hectorite was gradually added to
5.50 g of volatile silicone fluid (DC 245, ex. Dow Corning), whilst
shearing at a speed of ca. 8000 rpm on a Silverson L4RT mixer (ex.
Silverson, Chesham, Bucks.). After approximately 10 minutes, 0.18 g
of propylene carbonate was added dropwise to the mixture. After a
further 5 minutes of mixing at 8000 rpm, the mixture was removed
from the mixer and 0.89 g of DTPA was slowly stirred in. The
resulting liquid was mixed for a further 5 minutes and then sealed
into a tin plate can, having valve access, and 77.66 g of liquified
propellant (CAP 40, ex Calor) was introduced into the can from a
propellant `transfer can`, via the valve, using a polyethylene
transfer device. Finally, the can was fitted with a suitable
actuator to enable effective spray application of the product.
[0063] Example 2 (see Table 1B) was prepared in a similar manner to
Example 1, with the addition of poly(hexamethylenebiguanide)
stearate (PHMBS, as described in WO98/56252 [Unilever PLC and NV])
(previously passed through a 45 um sieve) at the same time as the
DTPA.
[0064] Comparative Examples A, B, and C (see Tables 1A and 1B) were
prepared in a similar manner to Examples 1 and 2, varying the
compositions as indicated.
Deodorancy Tests
[0065] The deodorancy performance of the compositions detailed
below were assessed using the following protocol:
[0066] A panel was employed comprising 50 individuals who had been
instructed to use control ethanolic deodorant products during the
week prior to the test. At the start of the test, panellists were
washed with unfragranced soap and test product (1.8 g total weight)
applied to one axilla and control product applied to the other (1.8
g total weight). (Product application was randomised to take into
account any left/right bias). Panellists were instructed not to
consume spicy food or alcohol, and not to wash under their own
axillae, during the duration of the test. A minimum of three expert
assessors determined the intensity of axillary odour at 5 hours and
24 hours after application, scoring the intensity on a scale of
1-5. After each 24 hour assessment, the panellists were re-washed,
and products re-applied, as above. The procedure was repeated 4
times. At the end of the test the data were analysed using standard
statistical techniques. The compositions tested and the mean
malodour scores observed are detailed in the following Tables. (It
must be noted that data illustrated in different Tables cannot be
directly compared, being derived using different panellists in
different tests.)
1TABLE 1A Antiperspirant vs. Antiperspirant + PHMBS.sup.1 Component
Example A Example B AACH.sup.2 5 5 DC245.sup.3 7.3 7.257 Bentone
38V.sup.4 0.5 0.5 Propylene carbonate.sup.5 0.2 0.2 PHMBS.sup.1 0
0.043 CAP40.sup.6 87 87 Mean 5 hour 1.83 1.91 malodour 24 hour 1.89
1.96 intensity.sup.7 All components are expressed as weight per
cent of the total composition. .sup.1Poly(hexamethylenebiguanide)
stearate. .sup.2Activated aluminium chlorohydarte, type A296, ex.
Guilini. .sup.3Volatile silicone, ex. Dow Corning.
.sup.4Structurant, quanternium-18-hectorite, ex. Rheox.
.sup.5Co-structurant. .sup.6Propellant, proprietary mix of butane,
isobutane and propane, Ex. Calor. .sup.7Differences in values not
significant at the 95% level. (Minimum differences required for
significance at the 95% and 99% confidence levels were: after 5
hours: 0.09 for 95% level; 0.12 for 99% level; after 24 hours: 0.10
for 95% level; 0.13 for 99% level.)
[0067] The results in Table 1A indicate that the addition of 0.043%
PHMBS anti-microbial to 5% AACH antiperspirant does not lead to an
improvement in the deodorancy performance.
2TABLE 1B Effect of Added Chelator Component Example C Example 1
Example 2 AACH 5 5 5 DC245 7.2 6.2 6.16 Bentone 38V 0.6 0.6 0.6
Propylene carbonate 0.2 0.2 0.2 DTPA.sup.1 0 1.0 1.0 PHMBS 0 0
0.043 CAP40 87 87 87 Mean malodour 5 hour 1.84 1.73 1.67
intensity.sup.2 24 hour 2.05 1.90 1.88 All components are expressed
as weight per cent of the total composition.
.sup.1Diethylenetriaminepentaacetic acid. .sup.2The difference in
mean malodour intensities between examples C and 2 was significant
at the 99% level after 5 hours. After 24 hours, the differences
between C and 1 and between C and 2 were both significant at the
99% level. (Minimum differences required for significance at the
95% and 99% confidence levels were: after 5 hours: 0.12 for 95%
level; 0.16 for 99% level; after 24 hours: 0.12 for 95% level; 0.15
for 99% level.)
[0068] The results in Table 1B indicate that the addition of 1%
DTPA chelator to 5% AACH antiperspirant leads to a significant
improvement in the deodorancy performance. In the presence of
0.043% additional anti-microbial (PHMBS) the difference is
significant after 5 hours, as well as after 24 hours. These latter
results are in marked contrast to the effect of added PHMBS in the
absence of chelator (Table 1A), where no benefit is observed.
[0069] The benefits observed after 24 hours indicate that prolonged
maintenance of malodour reduction results from the use of the
compositions of the invention; this is a direct result of the
prolonged anti-microbial activity of the compositions.
Anti-microbial Performance of Chelators
[0070] An axillary isolate of Staphylococcus epidermidis was grown
overnight in 100 ml of tryptone soy broth (TSB, Oxoid Ltd). 10 ml
of this culture was taken and subjected to centrifugation. The
separated cells were re-suspended in 10 ml of phosphate buffered
saline and the centrifugation procedure repeated. The washed cells
were re-suspended in 10 ml of phosphate buffered saline to give the
inoculum. 100 .mu.l of the inoculum was added to 100 ml of
semi-synthetic medium (SSM) containing (NH.sub.4).sub.2SO.sub.4
(0.066 g), MgSO.sub.4.7H.sub.2O (0.012 g), KCl (0.1 g),
KH.sub.2PO.sub.4 (0.27 g), Na.sub.2HPO.sub.4 (1.43 g), thiamin (0.1
mg), biotin (0.05 mg), Peptone P (0.05 g), and glucose (2.0 mmole)
which had been previously sterilised by autoclaving at 121.degree.
C. for 20 minutes. The pH of the SSM was adjusted to 6.7 with HCl
after sterilisation, prior to addition of the inoculum. This
control medium was utilised in all of the in vitro inhibition
studies. The chelator-containing test media were prepared in a
similar manner, the chelator being introduced at a concentration of
3.times.10.sup.-6 mol.dm.sup.-3 before the pH adjustment with
HCl.
[0071] 100 .mu.l of the S. epidermidis inoculum was introduced into
the control medium and into test media containing the chelators
indicated in Table 2. The cultures were inoculated at 37.degree. C.
(with agitation at 200 rpm) for 16 hours, and the optical density
of the cultures measured at 600 nm to determine the extent of
bacterial growth. By comparison of the optical density of the
culture in the presence of chelating agent, to that of the control,
the percentage inhibition of growth was established. (Optical
density measurements were made on 1 in 4 dilutions of the cultures
with 0.9% (w/v) saline, using 1 cm path length cuvettes, on a
Pharmacia Biotech Ultrospec 200 Spectrophotometer.)
3TABLE 2 Results of Anti-microbial Performance Tests Chelator
Inhibition of growth (%) EDTA 0 CDTA 12.3 DTPA 56.5 TTHA 56.3
[0072] These results indicate that DTPA and TTHA meet the criterion
to be considered preferred "micro-molar active" chelators, whilst
CDTA and EDTA fail this criterion.
Preparation of Stick Antiperspirant Deodorants
[0073] The stick antiperspirant deodorant compositions indicated in
Table 3 were prepared in the following manner. The stearyl alcohol,
hydrogenated castor oil, volatile silicone DC245, and PEG-8
distearate were heated under reflux at 85.degree. C., with
stirring, until all solids were melted. To the mixture was added
Suprafino talc and the antiperspirant salt. For Examples 3 and 4,
the DTPA and Cosmocil stearate were added at this point. Stirring
was continued and the temperature was allowed to fall to 60.degree.
C. On attainment of this temperature, the compositions were
transferred to plastic stick barrels and left to solidify.
[0074] The deodorancy performance of Example 3 and Comparative
Example D were assessed using the aforementioned protocol, with the
modification of using only 25 panellists and a product dosage of
0.30 g per axilla.
4TABLE 3 Stick Deodorant Antiperspirants Example Component D 3 4
AZAG.sup.1 25.0 25.0 25.0 Suprafino Talc 3.2 3.2 3.2 Stearyl
alcohol.sup.2 14.0 14.0 14.0 Hydrogenated Castor Oil.sup.3 4.0 4.0
4.0 PEG-8 distearate.sup.4 1.0 1.0 1.0 DTPA 0 1.0 3.0 Cosmocil
Stearate.sup.5 0 0.215 0.215 Volatile Silicone DC245.sup.6 to 100
to 100 to 100 Mean malodour 5 hour 1.60 1.41 -- intensity.sup.7 24
hour 1.77 1.70 -- All components are expressed as weight per cent
of the total composition. .sup.1Antipersprant salt: AZAG Q5-7167.
.sup.2Lanette C-18 DEO. .sup.3Castorwax MP80. .sup.4Estol E040DS.
.sup.5Polyhexamethylene biguanide. .sup.6Cyclomethicone. .sup.7the
Difference after 5 hours was significant at the 95% level. (Minimum
differences required for significance at the 95% and 99% confidence
levels were: after 5 hours: 0.16 for 95% level; 0.20 for 99% level;
after 24 hours: 0.14 for 95% level; 0.18 for 99% level.)
* * * * *