Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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STABILIZED WHITENING COMPOSITIONS AND METHOD OF PREPARING SAME
Field of the Invention
The present invention relates to useful pharmaceutical and cosmetic
compositions capable of
causing a whitening affect on the skin. In particular, the invention relates
to a stabilized composition
of hydroxyacid and a whitening agent together in solution capable of
maintaining the independent pH
values of its contents as well as other properties of the whitening agent and
hydroxyacid.
Background of the Invention
In recent times, cosmetics have developed beyond the mere concept of
ornamentation for the
face. Consumers now demand more from their makeup than simple color, coverage
or moisturizing.
For example, the ability to "whiten'' the skin is a desirable function for
some consumers. This may
I 0 be to remove freckles or other dark blemishes on the skin or it may be a
cultural preference. The color
of the skin is determined by melanin which is a biopolymer pigment
manufactured by special dendritic
cells known as melanocytes. Melanocytes are located primarily below or between
basal cells of the
epidermis or upper layer of the skin. The basal layer is one of two main
layers of the epidermis. The
viable basal layer is at the bottom of the epidermis in contact with the
dermis. And, the second layer
I 5 is the dead corneal or horny layer located above the basal layer which
extends upward to the surface
of the skin.
Characterized as unicellular "glands," melanocytes have long, thin, branching,
streamer-like
dendrites or arms that reach between the epidermal cells in their immediate
vicinity. An arrangement
of epidermal cells is thereby created around each melanocyte. The activity of
melanocytes determines
20 the production of melanin and therefore, the color or rather the light or
dark complexion of the skin.
Melanin production is stimulated by both internal and external factors.
Melanin once
produced, travels from the melanosome region to the dendrites of the
melanocyte. Epidermal cells
in contact with the melanin-laden dendrites phagocytose the tips of the
dendrites and transfer melanin
to the surrounding epidermal cells. Melanin granules move above the cell
nucleus inside the
25 epidermal cells. Because melanin orients itself in this manner, it is
believed that melanin functions
to protect cells from damaging ultraviolet ("UV") rays. Production of melanin
is stimulated by the
external factor of UV radiation.
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Internally, biochemical stimulation of melanin is achieved by the enzyme
tyrosinase.
Tyrosinase causes oxidation of substrates tyrosine and levodopa to dopaquinone
followed by
subsequent polymerization of numerous intermediates into melanin. The
mechanism of melanin
biosynthesis is a complex process and it is well known that tyrosinase is an
important driving force
in the process. See M.M. Wick, V.J. Hearing and H. Rorsman, Biochemistry
ofMelanization, pp. 251-
256 (1993). External factors such as UV radiation mentioned above also play a
role in the synthesis
of melanin by stimulating melanocytes to produce melanin. However, there is
current research
indicating that tyrosinase activity is inhibited by UV radiation and allows
rapid stimulation of pigment
production.
A number of prior art methods and compositions have been developed which
attempt to cause
a depigmentation effect on the skin. Many of the compositions useful for
inducing a depigmentation
effect on the human skin known in the prior art focus on bleaching the skin
with sodium hypochlorite,
hydroquinone, monoethyl ether, ammoniated mercury, zinc peroxide, mercurous
chloride or bi-
chloride of mercury. These compounds, however, are disadvantageous because
they sensitize the skin,
irritate the skin and do not provide predictable results. Therefore, an
effective treatment is still desired
that will inhibit either the production of the enzyme tyrosinase or the
production of the intermediates
during melanogenesis.
Compounds which inhibit synthesis of melanin include a serotonin uptake
antagonist and a
histamine agonist. The serotonin uptake antagonist, 6-nitroquipazine, inhibits
melanin activity without
affecting tyrosinase activity. And, the histamine agonists decrease and
eventually halt melanin
production by affecting tyrosinase activity. In addition to these two
compounds, ascorbic acid and its
derivatives are known to be useful in decomposing melanin in the epidermis.
Ascorbic acid has been
widely employed in skin whitening products. However, there are many challenges
to formulating
ascorbic acid due to the fact that in typical formulations, it can be quite
unstable and readily degrades.
Ascorbic acid is an alpha keto lactone and is sensitive to light, oxygen and
water due its low pH value.
Because the pH of the skin is about 5.5, use of ascorbic acid on the skin can
also be irritating.
However, to formulate ascorbic acid at a higher pH would cause it to degrade
and fail to provide the
desired whitening activity.
Another challenge in formulating ascorbic acid is its instability when
combined with other
actives or ingredients in a composition. The very reason for using various
actives and ingredients in
the formulation, i.e., their biological activity, can be subject to reduction
or loss of potency if they are
not combined in the proper vehicle. Consequently, a number of routinely
encountered factors can
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inactivate ascorbic acid in a formulation before it ever reaches the consumer.
It is difficult to avoid
the effects ofoxygen and UV light, as they are ubiquitous in nature. Thus,
there continues to be a need
for an acceptable vehicle capable of stably containing ascorbic acid and its
derivatives in combination
with other actives and ingredients, while protecting them from loss of their
desired properties.
Developing pharmaceutical and cosmetic compositions for the effect of
whitening can present
a serious problem to the formulator because substances have varying
properties. In particular,
substances having varying pH values when combined can neutralize each other
such that the desired
effect of the individual substances cannot be obtained. The individual
substances lose their desired
properties or can no longer provide the properties they were intended to have
when added to the
solution. To combat this problem, such compositions contain substances of
similar pH values.
Typically, when formulating ascorbic acid, the pH of the solution must be
below a pH value of about
3.5. However, as mentioned above, the acidity of the solution does not render
the solution suitable
for use as a cosmetic or pharmaceutical because it can irritate the skin.
Another method to overcome the problem of low pH is the use of a metal salt of
a
phosphorylated ascorbic acid. Particularly, magnesium ascorbyl phosphate
("MAP") which is only
stable at a pH value of about 8 or 9 is used as a whitening agent. However,
the pH of a solution
containing MAP is basic and when used on the skin is also irritating to the
skin. Further, it is difficult
to formulate a composition that contains MAP and other ingredients having a
low pH value. Because
of the need for a higher pH value, MAP cannot easily be combined with other
useful actives which
may have a lower pH value.
Additional difficulties arise with the formulation of ascorbic acid for
efficient application to
the skin. It is believed that ascorbic acid causes melanin to decompose in the
epidermis rendering a
"whitening" affect on the skin. Standard formulations are usually creams or
lotions from which
ascorbic acid must diffuse from the base formula to the skin to "whiten" the
skin.
Although ascorbic acid and its derivatives have been shown to be an effective
skin whitener,
their stability in combination with other actives and ingredients in solution
is a need that remains to
be addressed. Further, a vehicle is needed to enhance the delivery of ascorbic
acid from the base
formula to the skin. Therefore, in order to fully exploit its useful
properties as a whitener, a means
is sought by which ascorbic acid and its derivatives can be stabilized in a
desired composition with
other actives and ingredients, while retaining their independent useful
properties, and by which
ascorbic acid can be readily delivered from the formula to the skin. The
present invention provides
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such a means, and is substantially non-irritating to the skin. The demand for
whiteners that are
cosmetically appealing continues to grow and therefore, there is a need for a
stable whitening
composition that satisfies consumer needs.
SUMMARY OF THE INVENTION
The present invention provides stable cosmetic and pharmaceutical compositions
comprising
at least one hydroxyacid encapsulated in a lamellar vesicle and a whitening
agent in a cosmetically
or pharmaceutically acceptable carrier. Preferably the whitening agent is
optimally stable at non-
acidic pH levels. The encapsulated hydroxyacid provides for adequate stability
of the whitening
composition by allowing the hydroxyacid and the whitening agent to coexist in
solution together.
Therefore, the properties of the acid and the whitening agent do not degrade
while they are in solution
together.
The composition of the present invention can also contain two hydroxyacids.
Each of the
hydroxyacids are encapsulated within a lamellar vesicle. The individual
vesicles containing individual
hydroxyacids are combined in solution with a metal salt of a phosphoric acid
ester of ascorbic acid.
The metal salt can be formed by a univalent, divalent, or trivalent metal.
The invention also provides a method for preparing a stable cosmetic or
pharmaceutical
composition for causing a whitening affect on the skin, comprising
encapsulating at least one
hydroxyacid and adding the encapsulated hydroxyacid to a solution containing
an effective amount
ofa whitening agent. Further, the invention relates to a method of whitening
the skin which comprises
applying to the skin an effective amount of the subject whitening composition.
DETAILED DESCRIPTION OF THE INVENTION
The addition of hydroxyacids to whitening compositions is frequently desirable
because of
their properties. In addition to being an excellent exfoliating agent,
hydroxyacids can assist in
bringing about a whitening affect, thereby enhancing the efficacy of the
composition as a whole by
complementing the action of the main whitening active. In the present
invention, hydroxyacid is
encapsulated in a lamellar vesicle to provide a means for adding an acid
component to the whitening
composition containing whitening agents that otherwise may degrade the
properties of the acid, the
whitening agent, or both. Bv encapsulating the hydroxyacid in the vesicle, the
acid and the whitening
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agent can exist in solution together without affecting their desired
properties. Therefore, the solution
can contain numerous actives and other ingredients having various properties
that exist independently
in the solution. As a result, the composition is multifunctional in its effect
when applied to the skin.
A preferred composition of the present invention is a cosmetic or
pharmaceutical composition,
in which the total amount of hydroxyacid is preferably from about 0.01 to
about 5 percent, more
preferably from about 0.02 to about 1.0 percent. The term "hydroxyacid" for
purposes of the present
invention includes both alpha-hydroxyacids and beta-hydroxyacids in their free
acid form, as well as
covalent derivatives thereof. Suitable hydroxyacids include, but are not
limited to, alpha-hydroxyacids
such as lactic acid, glycolic acid, citric acid, alpha-hydroxyoctanoic acid,
alpha-hydroxydecanoic acid,
alpha-hydroxylauric acid, tartaric acid, glucouronic acid, galactouronic acid,
alpha-hydroxybutyric
acid, alpha-hydroxyisobutyric acid, malic acid, mandelic acid, pyruvic acid,
and tartronic acid,
preferably alpha-hydroxydecanoic and alpha-hydroxyoctanoic acids; and beta-
hydroxyacids such as
salicylic acid. Suitable covalent derivatives include esters, amides and
lactones, and mixtures thereof.
1 S The lamellar vesicles containing hydroxyacids in the amount stated above
may be present in
the composition in an amount of about 0.04 to about 20 percent by weight. In a
preferred
composition, the total amount of encapsulated hydroxyacid is preferably from
about 2 to about 10
percent by weight.
The use of lamellar vesicles to encapsulate and deliver both cosmetic and
pharmaceutical
actives has long been established. These vesicles contain multiple lipid
layers, each of which surround
a small aqueous volume separating the layer. Vesicles of this kind and methods
of making the same
have been described in, for example, U.S. Patent No. 5,585,109. The contents
are incorporated by
reference in its entirety.
The lamellar vesicle encapsulating the hydroxyacids is a lipid vesicle having
lipid
components. The term "lipid vesicle" for purposes of the present invention
refers to any spherical,
self closed structure composed of one or more lipid components arranged in the
form of curved lipid
bilayers which entrap part of the solvent in which they freely float. Lipid
vesicles are also commonly
referred to as "liposomes" and may consist of one or several concentric
membranes. While the
thickness of the membrane is about 4 manometers, the size of the liposome can
range from about 20
5
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nanometers to several dozen micrometers. Liposomes are essentially microscopic
spherical membrane
enclosed vesicles or sacs that are non-toxic to living cells and capable of
delivering their contents.
The contents of a liposome are contained by the bilayers of the liposome.
Phospholipids are
a common lipid source for the bilayers of the liposome. The liposomes of the
present invention may
be made from natural and synthetic phospholipids, glycolipids and other lipids
and lipid congeners;
cholesterol, cholesterol derivatives and other cholestero) congeners; charged
species which impart a
net charge to the membrane; reactive species which can react after liposome
formation to link
additional molecules to the liposome membrane; and other lipid soluble
compounds which have
chemical or biological activities. Examples of phospholipids include but are
limited to natural sources
such as egg yolk lecithin, soya lecithin, phosphatidylethanolamines,
phosphatidylserines, cereamides,
cerebrosides. and phosphatidylglycerides. The present invention also includes
alternatives to natural
phospholipids for example, synthetic phospholipids such as
dipalmitoylphosphatidylcholine, synthetic
amphiphiles such as polyglycerol derivatives, non-ionic materials such as
polyoxyethylene ethers and
esters, and cationic materials.
Liposomes are artificially made by a variety of methods. Most methods of
making lipid
vesicles are derived from the Bangham method, see Bangham et al., J. Mol.
Biol., 13:238-252 {1965).
A more detailed discussion on lipid vesicles is provided in the following
reference, D.D. Lasc,
"Liposomes, From Physics To Applications," (Elsevier, New York, 1993),
incorporated herein by
reference. The liposomes of the present invention may be of various size and
may comprise either one
or several membrane layers separating the internal and external compartments.
Whitening agents can include licorice extract, ascorbic acid (Vitamin C) or an
isomer,
homolog, analog or derivative thereof, salicylic acid, lactic acid, tyrosinase
inhibitors (e.g. kojic acid),
antioxidant free radical traps, compounds which inhibit cyclic AMP, histamine
agonists, serotonin
uptake inhibitors, pituitary-ovarian axis suppressors, Vitamin E.
Although the composition of the present invention can contain any whitening
agent, a
particular benefit is obtained when the whitening agent is one which is active
at a non-acidic pH.
Particularly preferred of this type are ascorbic acid derivatives. The
derivatives of ascorbic acid which
may be used are, for example, ascorbyl esters of fatty acids, such as ascorbyl
palmitate, ascorbyl
dipalmitate, ascorbyl dimethylsilanol palmitate, and ascorbyl stearate;
univalent, divalent or trivalent
metal or metal phosphate salts, such as magnesium, calcium, sodium, or
potassium ascorbyl
phosphate, or magnesium, calcium, sodium or potassium ascorbate. This
component is typically
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present in an amount of from about 0. I to about 10 percent by weight, more
preferably from 2 to about
4 percent. In a preferred embodiment of the present invention ascorbic acid is
a univalent, divalent
or trivalent metal salt of a phosphoric acid ester of ascorbic acid. In a most
preferred embodiment,
ascorbic acid is a derivative thereof in the form of a divalent metal salt of
a phosphoric acid ester of
ascorbic acid selected from the group consisting of magnesium or calcium.
These can be used singly
or in combinations of two or more.
In a particularly preferred embodiment, the whitening composition of the
present invention
is comprised of at least two hydroxyacids encapsulated in separate lamellar
vesicles in combination
with a metal salt of a phosphoric acid ester of ascorbic acid. Preferably, one
of the two hydroxyacids
is an alpha-hydroxyacid and the other is a beta-hydroxyacid. More preferably,
the composition
contains lactic acid and salicylic acid which enhance the properties of the
composition. Specifically,
lactic acid and salicylic acid enhance the ability of the composition to
whiten the skin. Further,
salicylic acid acts as a keratolytic agent increasing the rate of cell
turnover and providing an
exfoliating property to the composition.
The encapsulation ofthe hydroxyacids is an important feature ofthe present
invention because
it is the means by which hydroxyacids, which are acidic, stably exist in
solution with the whitening
agent which has a higher pH. Encapsulating the hydroxyacids also serves to
keep them in the most
effective layer of the skin. If more than one hydroxyacid is used, they may be
added to the
composition in a single liposome, or in separate individual iiposomes, which
may be of any type.
However. in a preferred embodiment, if salicylic acid is employed, it is
incorporated into a liposome
specifically adapted for delivery of salicylic acid. The appropriate vesicle
for encapsulating salicylic
acid is one that is designed slightly different than a liposome containing
lactic acid in order to
accommodate some of the challenges of encapsulating salicylic acid.
Accordingly, the liposome
containing salicylic acid, also known as a SalisomeTM, includes a membrane
forming a liposomal
bilayer surrounding the salicylic acid, a polar, water-soluble organic base,
and water.
Preparation of suitable SalisomesT'", is described, for example, in U.S.
Patent No. 5,585,109
the contents of which are incorporated herein by reference. To prepare the
liposomes containing lactic
acid, various methods can be used. There are numerous techniques for making
liposomes containing
lactic acid. In general, these techniques involve mixing the components that
form the lipid bilayer of
the liposome, as well as the component, in this case lactic acid, which is to
be encapsulated within the
liposome, under conditions that permit its formation. Further, the ingredients
used to make the
liposome can be processed in a microfluidizer to mass manufacture the
liposomes in a stable lamellar
7
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phase. Microfluidization permits the formation of liposomes that can maintain
an ordered lipid bilayer
during storage. The use of suitable microfluidizers for making lameilar
vesicles is described in
Mayhew et al., "Characterization of Liposomes Prepared Using a
Microemulsifier." Biochem. et
Biophys. Acta., 775, pp. 169-74 ( 1984).
For topical application, the whitening compositions can also be formulated
with a variety of
cosmetically and/or pharmaceutically acceptable carriers. Accordingly, the
compositions of the
present invention will comprise a pharmaceutically or cosmetically acceptable
carrier, in an amount
appropriate to accommodate the other components of the formulation. The term
"pharmaceutically
and/or cosmetically acceptable can ier" refers to a vehicle, for either
pharmaceutical or cosmetic use,
which vehicle delivers the active components to the intended target and which
will not cause harm to
humans or other recipient organisms. As used herein, "pharmaceutical" or
"cosmetic" will be
understood to encompass both human and animal pharmaceuticals or cosmetics.
The carrier may be
in any form appropriate to the mode of delivery, for example, solutions,
colloidal dispersions,
emulsions, suspensions, creams, lotions, gels, foams, mousses and the like.
The whitening compositions can be prepared in any form convenient for topical
application to
the skin. Such forms include, but are not limited to gels, creams,
dispersions, emulsions (water-in-oil
or oil-in-water), suspensions, lotions, foams, mousses and the like. In a
preferred embodiment, the
carrier is a suspension, dispersion or emulsion. The emulsion may be an oil-in-
water emulsion, or a
water-in-oil emulsion. These emulsions contain one or more oil components, an
aqueous component,
and a specific emulsifier component chosen depending on the nature of the
desired emulsion.
The oil component may be any pharmaceutically or cosmetically acceptable
material which
is substantially insoluble in water. These materials can be found for example
in the CTFA
International Dictionary of Cosmetic Ingredients as well as the U.S.
Pharmacopoeia or other
equivalent sources. Suitable oil components include, but are not limited to,
natural oils, such as
coconut oil; hydrocarbons, such as mineral oil and hydrogenated polyisobutene;
fatty alcohols, such
as octyldodecanol; esters, such as C12-15 alkyl benzoate; diesters, such as
propylene glycol
dipelargonate; triesters, such as glyceryl trioctanoate; sterol derivatives,
such as lanolin; animal waxes,
such as beeswax; plant waxes, such as carnauba; mineral waxes, such as
ozokerite; petroleum waxes,
such as paraffin wax; synthetic waxes, such as polyethylene; and mixtures
thereof. Suitable oil
components may also be silicones including, but not limited to, volatile
silicones such as
cyclomethicone; polymeric silicones such as dimethicone; alkylated derivatives
of polymeric silicones,
such as cetyl dimethicone and lauryl trimethicone; hydroxylated derivatives of
polymeric silicones,
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such as dimethiconol; and mixtures thereof. The aqueous component refers to
any pharmaceutically
or cosmetically acceptable material consisting essentially or predominantly of
water.
For preparation of an oil-in water emulsion, the oil-in-water emulsifier will
be an emulsifier
having a hydrophilic-lipophilic balance (HLB) of at least 8, or a mixture of
such emulsifiers with one
or more water-in-oil emulsifiers (i.e., emulsifiers having an HLB of from
about 2 to about 6), in which
case the type and amount of each emulsifier present in the mixture is selected
such that the effective
HLB of the resultant oil-in-water emulsifier component is at least about 6.
Techniques for combining
and ascertaining the effective HLB of a mixture of emulsifiers are known; see
L.M.Prince, in M.G.
DeNavarre, "The Chemistry and Manufacture of Cosmetics", Volume III, Second
Ed., (Continental
Press, Orlando, 1975), pp. 25-37.
Suitable oil-in-water emulsifiers include, but are not limited to, sorbitol
derivatives, such as
sorbitan monolaurate and polysorbate 20; ethoxylated alcohols such as laureth-
23, ethoxylated fatty
acids such as PEG-1000 stearate; amidoamine derivatives such as
stearamidoethyl diethylamine;
sulfate esters such as sodium lauryi sulfate; phosphate esters such as DEA
cetyl phosphate; fatty acid
I S amine salts such as TEA stearate; and mixtures thereof.
The emulsion may also be a water-in-oil emulsion. For this purpose, a water-in-
oil emulsifier
refers to any cosmetically acceptable emulsifier having an HLB of no greater
than 6, preferably from
about 2 to about 4. Suitable water-in-oil emulsifiers include, but are not
limited to, sorbitan
derivatives such as sorbitan laurate and sorbitan palmitate; alkoxylated
alcohols such as laureth-4;
hydroxylated derivatives of polymeric silicones, such as dimethicone copolyol;
alkylated derivatives
of hydroxylated polymeric silicones, such as cetyl dimethicone copolyol;
glyceryl esters such as
polyglyceryl-4 isostearate; beeswax derivatives such as sodium isostearoyl-2
lactylate; lecithin; and
mixtures thereof.
Because of the skin enhancing effects of the whitening compositions of the
present invention,
they may also have incorporated active agents which are used for skin
treatment, or which are
routinely applied topically. Examples of such active agents which may form
part of the composition
include, but are not limited to, those that improve or eradicate age spots,
keratoses and wrinkles,
analgesics, anesthetics, anti-acne agents, antibacterials, antiyeast agents,
antifungal agents, antiviral
agents, antidandruff agents, antidermatitis agents, antipruritic agents,
antiemetics, antimotion sickness
agents, anti-inflammatory agents, antihyperkeratolytic agents, anti-dry skin
agents, antiperspirants,
antipsoriatic agents, antiseborrheic agents, hair conditioners and hair
treatment agents, antiaging
9
*rB
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agents, antiwrinkle agents, antiasthmatic agents and bronchodilators,
sunscreen agents, antihistamine
agents, wound-healing agents, vitamins, corticosteroids, or hormones. More
specific examples of
useful active agents include retinoids, topical cardiovascular agents,
clotrimazole, ketoconazole,
miconozole, griseofulvin, hydroxyzine, diphenhydramine, pramoxine, lidocaine,
procaine,
mepivacaine, monobenzone, erythromycin, tetracycline, clindamycin,
meclocyline, hydroquinone,
minocycline, naproxen, ibuprofen, theophylline, cromolyn, albuterol, retinoic
acid, 13-cis retinoic
acid, hydrocortisone, hydrocortisone 21-acetate, hydrocortisone 17-valerate,
hydrocortisone 17-
butyrate, betamethasone valerate, betamethasone diproprionate, triamcinolone
acetonide, fluocinonide,
clobetasol, proprionate, benzoyl peroxide, crotamiton, propranolol,
promethazine, vitamin A
palmitate, vitamin E acetate and mixtures thereof. The amount of active agent
to be used in any given
formulation is readily determined in accordance with its usual dosage.
In addition to those components specifically noted above, the compositions may
also comprise
additional preservatives, fragrances, emollients, antiseptics,
antiinflammatories, antibacterials,
stabilizers, antioxidants, vitamins, pigments, dyes, humectants, and
propellants, as well as other
classes of materials the presence of which in the compositions may be
cosmetically, medicinally, or
otherwise desired. Such components can be found in the CTFA International
Cosmetics Ingredients
Dictionary, supra. Preservatives employed, may be in an amount of from 0.01-
2%, preferably from
0.01-I%, ofthe formula weight. Examples of suitable preservatives are BHA,
BHT, propyl paraben,
butyl paraben or methyl paraben or an isomer, homolog, analog or derivative
thereof.
The whitening compositions of the present invention can be topically applied
for spot
treatment. For example, the composition can be applied to areas of uneven skin
tones, dark spots or
freckles when they appear or on a continuing as needed basis. However, a
preferred method of
obtaining the benefits of the whitening composition is via chronic topical
application of a safe and
effective amount of the whitening composition of the present invention. It is
suggested as an example,
ZS that topical application range from about every other day to about 1 to 3
times daily, preferably from
about once daily to about 2 times daily, most preferably about once or twice
per day. By "chronic"
application, it is meant herein that the period of topical application may be
over the lifetime of the
user, preferably for a period of at least about one month, more preferably
from about three months to
about twenty years, more preferably from about six months to about ten years,
more preferably still
from about one year to about five years, thereby resulting in the achievement
of a whitening effect on
the skin. It will be recognized by those skilled in the art that the treatment
regimen employed can vary
depending upon the user's level of melanocyte activity producing melanin and
enzymatic activity
destroying melanin.
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Further, while the compositions of the present invention are ideal for spot
treatment they can
be used on the entire face if needed or they can be used on other areas of the
skin. The compositions
of the present invention are applied to the skin by covering the area desired
to be whitened and
blending the composition into such area of the skin. The whitening
compositions are preferably used
after a cleansing regimen. The cleansing regimen may consist of cleansing the
skin with a soap or
other form of cleanser, removing soap residue with a toner or clarifying
lotion, and applying a
moisturizing cream or lotion to the skin. Following these three general
cleansing steps, the whitening
compositions are applied to the desired areas of the skin to be whitened such
as areas of the skin where
the tone of the skin is uneven or other types of spots that may be found on
the skin.
The present invention is further illustrated by the following non-limiting
examples.
EXAMPLE I
Liposomes and SalisomesT"' (salicylic acid-containing liposomes) containing
lactic acid and
salicylic acid respectively are provided by Collaborative Laboratories, East
Setauket, NY. The
liposomes, SalisomesT"', and the whitening composition are prepared as
follows:
LIPOSOMES
Ingredient Percent
PHASE 1
Water 60%
Lecithin 3%
PHASE 2
Lactic Acid 15%
Phenonip 1
PHASE 3
Arginine 21
The ingredients in Phase I are mixed using vigorous stirring. The ingredients
of Phase
2 are added, and mixed together with Phase 1 ingredients. Next, the batch is
microfluidized
using a microfluidizer. After microfluidization, arginine is added.
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SALISOMESTM
Ingredient Percent
Water 74%
Arginine 13%
Salicylic Acid 10%
Tocopheryl acetate 1
Phenonip I
Soy phospholipids 1
The composition of the present invention which follows is obtained according
to the
procedure below. The following steps are performed successively at room
temperature (20°
C):
I. The constituents of PHASE I (hereinafter referred to as "the oil phase")
are mixed
together, followed by addition of the PHASE II constituent by sprinkling while
mixing with
a mixer.
2. Licorice is dissolved in butylene glycol and added to the oil phase.
3. Separately, the constituents of PHASE IV are mixed until they dissolved and
when clear,
liposome and SalisomeT'" are added and mixed until uniform; afterward, this
mixture is slowly
added to the oil phase while paddle mixing.
A pH test determines that the pH of the composition does not drift indicating
that the
liposome and the SalisomeT'" are stable. A lack of crystallization
substantiates further that
the magnesium ascorbyl phosphate is stable in the composition due to the
stability of the lactic
acid in the liposome and the salicylic acid in the SalisomeT"'.
WHITENING COMPOSITION
Ingredient Percent
PHASE I
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CA 02283574 1999-09-09
WO 99/36053 PCT/US98/22685
Cetyl dimethicone copolyol2%
Dioctyl sebacate 5.5%
Isohexadecane 7%
Dimethicone 6%
Polyglyceryl-3 diisostearate0.35%
PHASE II
Quaternium-18 Hectorite 1
PHASE I1I
Licorice extract 0.06%
Butylene glycol 4%
PHASE IV
Deionized water 59.088%
Magnesium ascorbyl phosphate3%
Parabens 1
Sodium citrate 2%
Citric acid 0.002%
PHASE V
Liposome 6%
SalisomeTM ~ 3%
100%
13
