Note: Descriptions are shown in the official language in which they were submitted.
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I
ANTI-ENZYME COIv>POSITIONS COMPRISING ETHYLENEDIAMINE DISUCCII~11C ACID
The invention relates to compositions, which can be administered or applied to
a human or
animal, to inhibit or reduce the enzyme activity.
Background
Various types of enzymes are present in the our body or on our skin, including
enzymes form
bacteria's, enzymes derived from our diet and enzymes produced by the body.
It is know that some of these enzymes can have undesirable side-effects. For
example, lipase
enzymes are present in the body exudates and these enzymes are known to cause
dermatitis or
skin rash, which for example, has always been a problem encountered by the
users of disposable
absorbent articles, such as diapers, incontinence articles, sanitary towels,
training pants etc.
Manufacturers of diapers and skin care products have developed various
products over the past -
decades which help reduce the occurrence of diaper rash (or skin rash). The
main focus thereby
has been to reduce the exposure of the skin to the body exudates. This is for
example done by
introduction to the diaper of absorbing or better absorbing materials. The
amount of water
which is in contact with the skin is thus reduced.
Lipase enzymes are also responsible for the production of fatty acids, which
are partially
eliminated from the body in the body exudates. These fatty acids can cause a
malodour of the
body.
EP 0117632-B relates to disposable articles which comprise lipase inhibiting
agents, preferably
zinc containing components, and a vehicle material. US 3,091,241 relates to
the use of triacetine
in vaginal tampons to inhibit lipase enzyme activity. US 3, 9b1,486 teaches
the use of adipic
acid to reduce the lipase enzyme activity and to reduce the skin rash.
It is known that the activity of various enzymes, such as lipase enzymes, is
depended on the
presence of certain metal ion, such as iron and copper, a so-called metallic
cofactor. It has been
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suggested to use EDTA complexing agents to react with the metallic cofactors,
to reduce the
enzyme activity (for example in NL 7506962).
However, it has been found that EDTA is not an effective complexing agents for
the metal ions
of the metallic cofactors, in particularly when other metal ions are present
on the skin or in the
compositions.
The inventors now found that certain complexing agents, in particular ethylene
diamine
disuccinic acid (EDDS), can very effectively inactivate or inhibit the
enzymes, by interacting
with the metallic cofactor, containing metal ions such as copper and iron, and
particularly when
other ions, such as calcium ions, are present. Since calcium ion
concentrations are generally
high in body exudates or on the surface of the skin or hair, the complexing
agents of the
invention will be more effective when administered to humans or animals or
applied to their
skin or hair, than known complexing agents such as EDTA.
Thus, for example, it has been found that the use of the complexing agents in
compositions of
the invention, results in a very effective reduction or a prevention of
dermatitis or malodour of
the body, also when calcium ions are present in the compositions or on the
skin, and for
example, it has been found that even very small amounts of these complexing
agents in these
compositions can effectively give the required prevention or reduction of
dermatitis or
malodour of the body.
Summary of the Invention
The invention provides a composition comprising ethylene diamine disuccinic
acid or a salt
(EDDS) for reduction of the enzyme activity, preferably of enzymes in contact
with the human
or animal body, in particular of enzymes present in the exudates.
The invention also provides compositions for reduction of the enzyme activity,
preferably of
enzymes in contact with the human or animal body, comprising a complexing
agent, and in use
additionally comprising calcium ions and one or more metal ions, selected from
the group
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consisting of Cu, Fe, Zn, Ni, Co (herein referred to as 'the selected metal
ions'), whereby the -
logl OCT is equal to or greater than the smallest value of A or B, where
A is -logl p(LT-MT) and B is K1 ( 1 - Kz ~ )(1 - K3.exp(-K4.P)),
CT is the total concentration of calcium ions, LT is the total concentration
of complexing
agent, MT is the total concentration of the metal ions, selected from the
group consisting of Cu,
Fe, Zn, Ni and Co; P is the pH of the composition, I is the ionic strength of
the composition,
wherein all concentrations are in moles/litre, where K1, K2, K3 and K4 are the
following
constants for the metals ions:
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Cup Fey Zn~ Nip Coy
K1 11.062 5.754 7.963 13.098 7.642
K2 0.496 0.479 0.619 0.535 0.652
K3 2.479 9385.0 24.202 1.473 32.069
K4 0.227 1.092 0.506 0.126 0.532
The invention also provides the use of the complexing agents as defined above
, including
ethylene diamine disuccinic acid or a salt (EDDS) for preparation of a
composition for
reduction of the enzyme activity, preferably of enzymes in contact with the
human or animal
body, in particular of enzymes present in the exudates.
Detailed Description of the Invention
The compositions of the invention reduce the enzyme activity of various
enzymes, which
require a metallic cofactor, in particular cofactors containing iron, copper,
cobalt, zinc or nickel-- ~---------
metal ions, by inhibiting or inactivating the enzymes.
The enzymes can be from bacteria's, fungi or algae, or can be produced by the
human or animal
body, or can be derived from the diet.
In particular esterase enzymes, including lipase enzymes, are very effectively
inhibited or
inactivated by the compositions of the invention.
The compositions can be used in any application where reduction of the enzyme
activity of
these enzymes is required. In particular, the compositions are used for
reduction of the enzyme
activity of enzymes in contact with the human or animal body, in particular
the skin.
According to a preferred aspect of the invention, in use a source of calcium
ions is also present ,
in the composition. Hereby is meant that the calcium ions can be present in
the composition
containing the EDDS prior to use or in use, the calcium ion can be introduced
in the
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compositions, e.g. by the application of the compositions to the skin, which
contains calcium
ions.
In a highly preferred aspect of the invention, the compositions are used for
reduction of the
enzyme activity of enzymes present in the exudates, in particular esterase
enzymes, including
lipase enzymes.
The compositions are particularly useful when calcium ions are present in the
compositions
and/ or in contact with the human or animal body.
In preferred embodiments of the invention, the compositions comprising the
complexing agents
are useful for the treatment of enzymatic dermatitis or the treatment of
formation of a malodour
of the body, caused by enzymes, in particular for reduction of the enzyme
activity of lipase
enzymes.
The compositions may be cosmetic compositions, preferably in the form of a
spray, cream,
foam, lotion, gel, oil, ointment or powder or tablet, preferably in the form
of a water-in-oil -''~ i'
emulsion.
Highly preferred are compositions are comprised in a deoderant or absorbent
articles, such as
diapers, wet wipes, as described herein.
By treatment is meant herein an improvement of the affected condition of the
human or animal
body, caused by the enzyme activity. Thus includes in one preferred aspect of
the invention, the
reduction or at least stabilisation of the malodour of the body , which is
caused by enzymes; in
another preferred aspect of the invention, the reduction or at least
stabilisation of the enzymatic
dermatitis or the rash of the skin, caused by enzymes.
The amount of the composition of the invention used for the reduction of the
enzyme activity or
in the treatment, will vary with the particular location of the condition
being treated, the
severity of the condition being treated, the expected duration of the
treatment, any specific
sensitivity to either the composition specific to the user, the condition of
the user, concurrent
therapies being administered, other conditions present in the user.
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For the present invention it is preferred that a minimum inhibitory
concentration of the
compositions containing the complexing agent is, preferably topically, applied
to act as a
complexing agent for selected metal ions present on the skin, which are
required by the
enzymes for their enzymatic performance, in an amount and form such that it is
available to
inhibit the activity of the enzymes present, particularly in the presence of
calcium ions.
The complexing agents or compositions are in particular useful for the
reduction of the enzyme
activity of esterase enzymes, and thus for inhibition or inactivation of
esterases, such as lipases
or lipolytic enzymes. Their general activity is to hydrolyse fats present in
the ester form (such
as the glycerides found in human skin), and accordingly generate fatty acids
and glycerol,
which can cause irritation and malodour of the body. Because this group of
enzymes is so
widely distributed in plants, moulds, bacteria, milk, and milk-products, as
well as in almost all
animal tissues, and because moreover human lipase enzymes are present in the
pancreatic
exudates, they are almost always present in or on the human or animal body.
The activity of these lipases contributes to almost all skin rash or in
particular diaper rash,
causing irritation by the digestive degenerative action of lipase on the skin
per se and by
breaking down the lipid skin-components compromises the barrier property of
the skin in the
affected area. This breakdown of the integrity of the skin allows other
components of the body
exudates (urine and faeces in particular), which may not, by themselves, be
irritating, to migrate
through the compromised skin. At this point normally harmless components may
then become
irritating.
Highly preferred additional components of the compositions of the invention
may be
bactericidal or fungicidal agents, and/ or other enzyme inhibitors. Highly
preferred can be the
inclusion of cationic organic compounds, such as cationic surfactants.
pH Measurement
The pH as used herein can be determined by any known method of calculating or
measuring the
pH of an aqueous solution.
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Ionic Strenrsth Measurement
The ionic strength (I) can be determined by the following equation:
I='/zEcizi2,
wherein c is the molecular concentration of the soluble ion (i) and z is the
charge of the soluble
ion (i).
Complexin;~ AA ent
A highly preferred complexing agent for use in compositions of the invention
is N, N'- ethylene
diamine disuccinic acid or its salt (EDDS).
It is known that the (S,S) EDDS isomer is more readily biodegradable than the
(R,R) isomer.
Thus, depending of the application of the aqueous compositions of the
invention, it may be
desirable to use only one of the isomers of EDDS. It may be preferred that a
racemic mixture
of the isomers is used in the aqueous compositions, for example because the
racemic mixture is
less expensive.
The exact level of incorporation of the complexing agents in the compositions
of the invention
will depend on the nature of the compositions and the mode of applications.
However, in
general even small amounts of complexing agents can be sufficient to obtain
the required
prevention or reduction of dermatitis. Typical amount of complexing agents can
be from
0.001 % by weight to 30% by weight, more preferably from 0.005% to 10%, more
preferably
from 001 % to 5% by weight of the composition..
Method of Preparation of the Compositions
The compositions can be prepared by any method known in the art for
preparation for cosmetic
compositions or medicament. The exact method will depend on the nature of the
composition.
The complexing agent can be added to the campositions in its acid or salt
form, or be combined
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with other ingredients commonly used in cosmetic compositions or medicaments,
or dispersed
or dissolved in water or oil or a water-in=oil emulsion prior to addition to
the composition.
Method of Use of Compositions
The composition of the invention can be administered to the patient or user by
any method
known in the art, but preferably the composition is applied to the skin or
hair, which will be in
contact with, or the vicinity of the enzymes.
The compositions can also be applied (firstly) to an article, such as a wipe
or tissue, which will
then be applied to the skin.
When the composition is used for treatment of malodour of the body, the
composition may
preferably be in the form of a deodorant composition, in the form of a fluid,
gel, cream or
powder, contained in a stick or spray .
Absorbent Articles
The compositions of the present invention can be comprised in an absorbent
article, preferably a
disposable absorbent article. Particularly preferred absorbent articles
therefor is a wipe or a
diaper. The diaper preferably comprises the composition in the topsheet of the
diaper.
As used herein, the term "absorbent articles" refers to devices which absorb
and contain body
exudates, and, more specifically, refers to devices which are placed against
or in proximity to
the body of the wearer to absorb and contain the various exudates discharged
from the body.
The term "disposable" is used herein to describe absorbent articles which are
not intended to be
laundered or otherwise restored or reused as an absorbent article (i.e., they
are intended to be
discarded after a single use and, preferably, to be recycled, composted or
otherwise disposed of
in an environmentally compatible manner).
The structure of the disposable absorbent article is not critical to the
practice of the present
invention.
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Normally, the composition is incorporated into the absorbent article or diaper
in particular in an
amount which will deliver the required treatment or reduction or inhibition of
the enzyme
activity, whereby it may be preferred that this is achieved after frequent
use.
The disposable absorbent article preferably contains the composition according
to the invention
at a level such that the complexing agents therein are present at a level of
from 0.01 % to 30%,
more preferably from 0.01 % to 10%, most preferably from 0.05% to 5% by weight
of the
article.
Additional In~~redients
The composition of the invention can comprise additional ingredients. Which
ingredients are
present and at which level depends on the character of the composition and the
use thereof.
Thus for example lotions will generally comprise different additional
ingredients to powders.
It can be preferred that the compositions comprise one or more other
ingredient which can
reduce dermatitis, or compounds which can help the healing of the skin, such
as vitamins
(vitamin E) and cortisone's, and also compounds to soften the skin such as
vaseline, glycerin,
triethyleneglycol, lanolin, paraffin and another group of polymers extensively
employed by
pharmaceutical and cosmetic manufactures, as also described herein.
Depending on the application of the compositions of the invention, a preferred
additional
ingredient can be one or more builders or dispersants. It can be preferred
that a crystal growth
inhibitor is present, preferably in addition to dispersants.
Suitable examples of water-soluble phosphates, suitable as crystal growth
inhibitors or builders,
are the alkali metal tripolyphosphates, sodium, potassium and ammonium
pyrophosphate,
sodium and potassium and ammonium pyrophosphate, sodium and potassium
orthophosphate,
sodium polymeta/phosphate in which the degree of polymerization ranges from
about 6 to 21,
and salts of phytic acid.
Any builder or dispersant material known in the art can be used. Particularly
useful builders or
dispersants can be monomeric, oligomeric and polycarboxylate-containing
components,
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polymeric components, borate-containing components and phosphate-containing
components
and silicate and aluminosilicate-containing components.
Suitable polycarboxylates or polycarboxylic acids can be succinic acid,
malonic acid,
(ethylenedioxy) diacetic acid, malefic acid, diglycolic acid, tartaric acid,
tartronic acid and
fumaric acid; citrates, aconitrates and citraconates as well as succinate
derivatives such as the
carboxymethyloxysuccinates described in British Patent No. 1,379,241,
iactoxysuccinates
described in British Patent No. 1,389,732, and aminosuccinates described in
Netherlands
Application 7205873, and the oxypolycarboxylate materials such as 2-oxa-1,1,3-
propane
tricarboxylates described in British Patent No. 1,387,447; oxydisuccinates
disclosed in British
Patent No. 1,261,829, 1,1,2,2-ethane tetracarboxylates, 1,1,3,3-propane
tetracarboxylates and
1,1,2,3-propane tetracarboxylates; sulfosuccinate derivatives disclosed in
British Patent Nos.
1,398,421 and 1,398,422 and in U.S. Patent No. 3,936,448, and the sulfonated
pyrolysed citrates
described in British Patent No. 1,439,000;
Polymeric components include the water soluble organic homo- or co-polymeric
polycarboxylic
acids or their salts in which the polycarboxylic acid comprises at least two
carboxyl radicals _,
separated from each other by not more than two carbon atoms. Polymers of the
latter type are
disclosed in GB-A-1,596,756. Examples of such salts are polyacrylates of MWt
1000-5000 and
their copolymers with malefic anhydride, such copolymers having a molecular
weight of from
2000 to 100,000, especially 40,000 to 80,000.
The polyamino components are useful herein including those derived from
aspartic acid such as
those disclosed in EP-A-305282, EP-A-305283 and EP-A-351629.
Terpolymers containing monomer units selected from malefic acid, acrylic acid,
polyaspartic
acid and vinyl alcohol, particularly those having an average molecular weight
of from 5,000 to
10,000, are also suitable herein.
Other polymeric components suitable for incorporation in the compositions
herein include
cellulose derivatives such as methylcellulose, carboxymethylcellulose,
hydroxypropylmethylcellulose and hydroxyethylcellulose.
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Further useful polymeric components are the polyethylene giycols, particularly
those of
molecular weight 1000-10000, more particularly 2000 to 8000 and most
preferably about 4000
Other preferred ingredients are amorphous or crystalline, preferably layered,
silicate or
aluminisilicate materials or builders. Suitable aluminosilicate zeolites have
the unit cell formula
Naz[(A102)z(Si02)y]. xH20 wherein z and y are at least 6; the molar ratio of z
to y is from 1.0
to 0.5 and x is at least S, preferably from 7.5 to 276, more preferably from
10 to 264. The
aluminosilicate materials are in hydrated farm and are preferably crystalline,
containing from
10% to 28%, more preferably from I 8% to 22% water in bound form.
Lotions, Creams, Oils, Foams, Ointments Gels Powders Tablets and the like
The present compositions can be used for any suitable purpose. In particular,
the present
compositions are suitable for topical application to the skin or hair. In
particular, the skin care
compositions can be in the form of creams, sprays, lotions, gels, and the
like. Preferably the
cosmetic compositions herein are in the form of an oil-in-water emulsion of
one or more oil
phases in an aqueous continuous phase, each oil phase comprising a single oily
component or a
mixture of oily components in miscible or homogeneous form but said different
oil phases
containing different materials or combinations of materials from each other.
The overall level
of oil phase components in the compositions of the invention is preferably
from about 0.1% to
about 60%, preferably from about I% to about 30% and more preferably from
about 1% to
about 10% by weight.
The present compositions preferably comprise, as either all or a portion of
the oil phase or oil
phases referred to above a first silicone-containing phase comprising a
crosslinked
polyorganosiloxane polymer and a silicone oil, wherein the composition
comprises 0.1 % to
about 20%, preferably from about 0.5% to about 10%, more preferably from about
0.5% to
about 5%, by weight of composition, of the combination of crosslinked silicone
and silicone oil.
Compositions herein preferably also comprise a second non-crosslinked silicone-
containing
phase. In preferred embodiments the second silicone-containing phase is
present in a level of
from about 0.1 % to about 20%, especially from about 0.1 % to about 10% by
weight of
composition.
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Suitable silicone fluids for use in the second silicone-containing phase
herein include water-
insoluble silicones inclusive of non-volatile polyalkyl and polyaryl siloxane
gums and fluids,
volatile cyclic and linear polyalkylsiloxanes, polyalkoxyIated silicones,
amino and quaternary
ammonium modified silicones, and mixtures thereof.
In preferred embodiments the second silicone-containing phase comprises a
silicone gum or a
mixture of silicones including the silicone gum. As used herein, the term
"silicone gum" means
high molecular weight silicone-based fluids having a mass-average molecular
weight in excess
of about 200,000 and preferably from about 200,000 to about 400,000. Silicone
oils generally
have a molecular weight of less than about 200,000. Typically, silicone gums
have a viscosity
at 25°C in excess of about 1,000,000 mm2.s-1. The silicone gums include
dimethicones as
described by Petrarch and others including US-A-4,152,416, May 1, 1979 to
Spitzer, et al, and
Noll, Walter, Chemistry and Technology of Silicones New York: Academic Press
1968. Also
describing silicone gums are General Electric Silicone Rubber Product Data
Sheets SE 30, SE
33, SE 54 and SE 76.
In preferred embodiments, another, third, oil phase is present in an amount of
from about 0.1%
to about 15%, more preferably from about 1% to about 10% by weight of
composition. The
third oil phase can be either a separate phase or can form one phase together
with either or both
of the first and second silicone phases. Preferably, the third oil phase is a
separate phase.
This oil phase preferably comprises a non-silicone organic oil, such as a
natural or synthetic oil
selected from mineral, vegetable, and animal oils, fats and waxes, fatty acid
esters, fatty
alcohols, fatty acids and mixtures thereof, which ingredients are useful for
achieving emollient
cosmetic properties.
Suitable first oil phase components for use herein include, for example,
optionally hydroxy-
substituted Cg-CSp unsaturated fatty acids and esters thereof, beeswax,
saturated and
unsaturated fatty alcohols such as behenyl alcohol and cetyl alcohol,
hydrocarbons such as
mineral oils, petrolatum and squalane, fatty sorbitan esters (see US-A-
3988255, Seiden, issued
October 26 1976), lanolin and lanolin derivatives, animal and vegetable
triglycerides such as
almond oil, peanut oil, wheat germ oil, linseed oil, jojoba oil, oil of
apricot pits, walnuts, palm
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nuts, pistachio nuts, sesame seeds, rapeseed, cade oil, corn oil, peach pit
oil, poppyseed oil, pine
oil, castor oil, soybean oil, avocado oil, safflower oil, coconut oil,
hazelnut oil, olive oil,
grapeseed oil, rhea butter, shorea butter, and sunflower seed oil and C 1 _C24
esters of dimer and
trimer acids such as diisopropyl dimerate, diisostearylmalate,
diisostearyldimerate and
triisostearyltrimerate. Of the above, highly preferred are the mineral oils,
petrolatums,
unsaturated fatty acids and esters thereof and mixtures thereof.
Amphiphilic Surfactant
A further preferred component of the compositions herein is an organic
amphiphilic surfactant
which is capable of forming smectic lyotropic crystals in product or when the
product is being
applied to the skin at ambient or elevated temperatures. Preferably the
amphiphilic surfactant is
capable of forming liquid crystals at a temperature in the range from about
20°C to about 40°C.
Preferably the amphiphilic surfactant is capable of forming smectic lyotropic
liquid crystals.
Once application of the product to the skin has been completed, liquid
crystals may not be
identifiable on the skin surface or stratum corneum. The amphiphilic
surfactant is preferably
present at a level of from about 0.1 % to about 20%, preferably from about 0.1
% to about 10%,
by weight.
Organic amphiphilic surfactants suitable for use herein include those having a
weight average
HLB (Hydrophilic Lipophilic Balance) in the range from about 2 to about 12,
preferably from
about 4 to about 8.
Preferred organic amphiphilic surfactants employed herein have a long
saturated or unsaturated
branched or linear Iipophilic chain having from about 12 to about 30 carbon
atoms such as
oleic, lanolic, tetradecylic, hexadecylic, isostearylic, lauric, coconut,
stearic or alkyl phenyl
chains. When the hydrophilic group of the amphiphilic material forming the
liquid crystal
phase is a nonionic group, a poiyoxyethylene, a polyglycerol, a polyol ester,
oxyalkylated or
not, and, for example, a polyoxyalkylated sorbitol or sugar ester, can be
employed. When the
hydrophilic group of the amphiphilic surfactant forming the liquid crystal
phase is an ionic
group, advantageously there can be used, as the hydrophilic group, a
phosphatidylcholine
residue as found in lecithin.
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The compositions can also comprise Amphoteric, anionic, nonionic and cationic
surfactants.
A wide variety of optional ingredients such as non-occlusive moisturizers,
humectants, gelling
agents, neutralizing agents, perfumes, colouring agents and surfactants, can
be added to the skin
compositions herein.
The compositions herein can comprise a humectant. Suitable humectants for use
herein include
sorbitol, propylene glycol, butylene glycol, hexylene glycol, ethoxylated
glucose derivatives,
hexanetriol, glycerine, glycine, hyaluronic acid, arginine, Ajidew (NaPCA),
water-soluble
polyglycerylmethacrylate lubricants and panthenols. A preferred humectant
herein is glycerine
(sometimes known as glycerol or glycerin). Chemically, glycerine is 1,2,3-
propanetriol and is a
product of commerce. One large source of the material is in the manufacture of
soap.
Glycerine is especially preferred in the compositions of the invention from
the viewpoint of
boosting moisturisation. Also preferred for use herein is butylene glycol.
Particularly preferred
from the viewpoint of boosting moisturisation is a combination of glycerine
and urea.
In the present compositions, the humectant is preferably present at a level of
from about 0.1% to
about 20%, more preferably from about 1% to about 15%, and especially from
about S% to
about 15% by weight of composition.
The compositions of the invention can also contain a hydrophilic gelling agent
at a level
preferably from about 0.01 % to about 10%, more preferably from about 0.02% to
about 2%,
and especially from about 0.02% to about 0.5%. The gelling agent preferably
has a viscosity
(1% aqueous solution, 20°C, Brookfield RVT) of at least about 4000
mPa.s, more preferably at
least about 10°000 mPa.s and especially at least 50,000 mPa.s.
Suitable hydrophilic gelling agents can generally be described as water-
soluble or colloidally
water-soluble polymers, and include cellulose ethers (e.g. hydroxyethyl
cellulose, methyl
cellulose, hydroxypropylmethyl cellulose), polyvinylpyrrolidone,
polyvinylalcohol, guar gum,
hydroxypropyl guar gum and xanthan gum.
Preferred hydrophilic gelling agents herein, however, are acrylic acid/ethyl
acrylate copolymers
and the carboxyvinyl polymers sold by the B.F. Goodrich Company under the
trade mark of
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Carbopol resins. These resins consist essentially of a colloidally water-
soluble polyalkenyl
polyether crosslinked polymer of acrylic acid crosslinked with from 0.75% to
2.00% of a
crosslinking agent such as for example polyallyl sucrose or polyallyl
pentaerythritol. Examples
include Carbopol 934, Carbopol 940, Carbopol 950, Carbopol 954, Carbopol 980,
Carbopol 951
and Carbopol 981. Carbopol 934 is a water-soluble polymer of acrylic acid
crosslinked with
about 1 % of a polyallyl ether of sucrose having an average of about 5.8 allyI
groups for each
sucrose molecule. A most preferred polymer is Carbopol 954. Also suitable for
use herein are
hydrophobically-modified cross-linked polymers of acrylic acid having
amphipathic properties
available under the Trade Name Carbopol 1382, Carbopol 1342 and Pemulen TR-1
(CTFA
Designation: Acrylates/10-30 Alkyl Acrylate Crosspolymer). A combination of
the polyalkenyl
polyether cross-linked acrylic acid polymer and the hydrophobically modified
cross-linked
acrylic acid polymer is also suitable and is preferred for use herein. The
gelling agents herein
are particularly valuable for providing excellent stability characteristics
over both normal and
elevated temperatures.
Neutralizing agents suitable for use in neutraiizing acidic group containing
hydrophilic gelling
agents herein include sodium hydroxide, potassium hydroxide; ammonium
hydroxide, -----
monoethanolamine, diethanolamine and triethanolamine.
Other optional materials include keratolytic agents/desquamation agents such
as salicylic acid;
proteins and polypeptides and derivatives thereof; water-soluble or
solubilizable preservatives
preferably at a level of from about 0.1 % to about 5%, such as Germall 1 I 5,
methyl, ethyl,
propyl and butyl esters of hydroxybenzoic acid, benzyl alcohol, EDTA, Euxyl
(RTM) K400,
Bronopol (2-broma-2-nitropropane-1,3-diol) and phenoxypropanol; anti-
bacterials such as
Irgasan {RTM) and phenoxyethanol (preferably at levels of from 0.1% to about
5%); soluble or
colloidally-soluble moisturising agents such as hylaronic acid and starch-
grafted sodium
polyacrylates such as Sanwet (RTM) IM-1000, IM-1500 and IM-2500 available from
Celanese
Superabsorbent Materials, Portsmith, VA, USA and described in USA-A-4,076,663;
vitamins
such as vitamin A, vitamin C, vitamin E and 'vitamin K; alpha and beta
hydroxyacids; aloe vera;
sphingosines and phytosphingosines, cholesterol; skin whitening agents; N-
acetyl cysteine;
colouring agents; perfumes and perfume solubilizers and additional
surfactants/emulsifiers such
as fatty alcohol ethoxylates, ethoxylated polyol fatty acid esters, wherein
the polyol can be
selected from glycerine, propyieneglycol, ethyleneglycol, sorbitol, sorbitan,
CA 02318780 2000-07-28 ~ , ,
WO 99/38484 PCTIIB99/00120
16
polypropyleneglycol, glucose and sucrose. Examples include glyceryl
monohydroxy stearate
and stearyl alcohol ethoxylated with an average of from 10 to 200 moles of
ethyiene oxide per
mole of alcohol and PEG-6 caprylic/capric glycerides.
The compositions of the present invention can also comprise a safe and
effective amount of
vitamins, such as vitamin E, B, preferably vitamin B3 vitamin a or retinoid.
The compositions
of the present invention preferably comprise from about 0.01 % to about 50%,
more preferably
from about 0.1% to about 10%, even more preferably from about 0.5% to about
10%, and still
more preferably from about 1% to about 5%, most preferably from about 2% to
about 5%, of
the vitamin.
The pH of the compositions is preferably from about 4 to about 9, more
preferably from about 6
to about 8Ø
The balance of the composition is water or an aqueous carrier suitable for
topical application to
the skin. The water content of the compositions herein is generally from about
30%xo about
98.89%, preferably from about 50% to about 95% and especially from about 60%
to about 90%
by weight.
The compositions of the invention are preferably in the form of a moisturising
cream or lotion,
which can be applied to the skin as a leave-on product.
