Title of Invention

OLEAGINOUS PHARMACEUTICAL AND COSMETIC FOAM

Abstract The invention relates to stable oleaginous cosmetic or therapeutic foam compositions containing certain active agents, having unique therapeutic properties and methods of treatment using such compositions. The foamable composition includes at least one solvent selected from the group consisting of: a hydrophobic solvent, a silicone oil, an emollient, a co-solvent, and mixtures thereof, wherein the solvent is present at a concentration of about 70% to about 96.5% by weight of the total composition, at least a non-ionic surface-active agent at a concentration of about 0.1 % to less than about 10% by weight of the total composition; at least one gelling agent at a concentration of about 0.1% to about 5% by weight of the total composition; a therapeutically effective amount of at least one active agent; and at least one liquefied or compressed gas propellant, at a concentration of about 3% to about 25% by weight of the total composition.
Full Text OLEAGINOUS PHARMACEUTICAL AND COSMETIC FOAM
FIELD OF THE INVENTION
[0001] The invention relates to oleaginous foam compositions including cosmetic or
therapeutic active agents, and methods of topical treatment using the compositions.
BACKGROUND OF THE INVENTION
[0002] Certain foam products for topical application of therapeutical agents and
cosmetics have been prepared as oil-in-water emulsions. Foams and, in particular, foam
compositions having a high oil content are complicated systems that do not form under
all circumstances. Slight shifts in foam composition, such as the addition of an active
ingredient, may destabilize the foam. It is known in the art that hydrophobic solvents are
difficult to formulate into a foam-producing product. Addition of conventional
hydrophobic solvents interferes with the foam forming ability of the surface active agent,
and thus, in the few foam products containing high-oil concentrations that have been
reported, high surface active agent concentrations are used, which may cause
undesirable irritation on one hand, and costly raw material usage on the other hand are
used.
[0003] Oleaginous formulations for the preparation of cosmetic and therapeutic
compositions are known in the art.
[0004] US Pat. No. 6,620,773 relates to a foaming oil composition, including a
surface active agent mixture and an oil component, the surface active agent mixture
containing an anionic or zwitterionic surface active agent, a nonionic surface active agent
and at least one ethoxylated alkyl phosphate ester component. The surface active agent
mixture ranges from about 15% to about 50% of the total composition, and that of the oil
component ranges from about 50% to about 85%.
[0005] US Pat. Nos. 5,700,396 and 5,589,515 disclose a cosmetic emulsion .
composition containing 0.1 to 99 wt% oily component (balance aqueous component).
The oily component includes at least 85% weight % of cis A9-octadecanoic acid or
derivatives thereof, which cis A9-octadecanoic acid or derivatives thereof serve as a
surface active agent in the formulation.
[0006] US Pat. No. 6,524,594 describes a gelled oil composition containing an
emulsifier, a gelling agent, an oil, and a surface active agent for producing a significant

amount of foam when, applied to the skin in the presence of water. The surface active
agent is used in an amount from about 10% to about 20%, and more preferably, from
about 15% to about 20%.
[0007] US Pat. No. 6,121,210 discloses foamable, silicone oil compositions and
methods of lubricating surfaces with such compositions. The compositions are oil-in-
water emulsions comprising silicone oil-in-water emulsion, a liquid propellant and a foam
builder comprising a solid, non-ionic lipophilic surface active agent having an HLB value
of about 3 to about 8. Foam stabiliziers including long claim fatty alcohols are included.
A propellant is included to create a foamable composition.
[0008] W091/11991 teaches an essentially non-aqueous and non-oily foamable
composition, that can be used for rectal administration of pharmaceuticals, comprising a
liquid polar polyol or polyol mixture, a pharmaceutically active ingredient and at least one
foam stabilizing and emulsifying surfactant. However, this foam composition is
associated with disadvantages and the purposes of the present invention are not
attained (see comparative example below).
[0009] In general, the foamable compositions of the art are based on oil-in-water
emulsions. Furthermore, they often include a high content level of surface active agents
and foaming agents required to form acceptable stable and posses low specific gravity
foams. Such surface active agents, and particularly ionic surface active agents, such as
anionic surface active agents (e.g. sodium lauryl sulfate (SDS)), may have adverse
affects on certain patients, including concentration-dependent skin irritation.
[0010] There remains an unmet need for improved, stable and non-irritating
oleaginous foam formulations, intended for dermal and mucosal delivery of
pharmaceutical and cosmetic, with unique therapeutic and cosmetic properties.
SUMMARY OF THE INVENTION
[0011] The present invention provides stable, oleaginous foam-forming compositions
including at least one active agent for dermal and mucosal delivery. The composition is
dispensed as a foam providing a stable product that is pleasant and easy to spread,
resulting in high patient compliance. The "oleaginous" composition has the organoleptic
character of an oily substance, i.e., an oily feeling, when topically administered to the
skin or mucosal tissue.
[0012] According to one aspect of the present invention, the composition includes:



a. a solvent selected from the group consisting of a hydrophobic solvent, a co-
solvent, and mixtures thereof, wherein the solvent is present at a concentration of about
70% to about 96.5% by weight of the total composition;
b. a surface-active agent at a concentration of about 0.1% to about 10% by
weight of the total composition;
c. optionally, a gelling agent at a concentration of about 0.1% to about 5% by
weight of the total composition;
d. an active agent in a therapeutically effective concentration; and
e. a propellant at a concentration of about 3% to about 25% by weight of the total
composition.
[0013] Water and optional ingredients are added to complete the total weight to
100%, although the composition may be essentially free of lower alkyl alcohols. In one
or more embodiments, the oleaginous composition of the present invention contains less
than about 5% of a short chain alcohol having up to 5 carbon atoms in its carbon chain
skeleton.
[0014] In one or more embodiments, the oleaginous composition includes water at a
concentration less than about 30%, preferably less than about 20%, more preferably less
than about 10% by weight.
[0015] In one or more embodiments, the oleaginous composition of the present
invention further includes a foam adjuvant.
[0016] In yet other embodiments, the oleaginous composition of the present
invention forms a water in oil emulsion.
[0017] In one or more embodiments, the oleaginous composition of the present
invention includes a hydrophobic solvent having solubility in distilled water at ambient
temperature of less than about one gram per 100 ml. The hydrophobic solvent may be a
mineral oil, MCT oil, triglyceride oil, silicone oil, a polyunsaturated oil, an unsaturated oil
and an essential oil, and mixtures thereof.
[0018] In one or more embodiments, the oleaginous composition includes a co-
solvent. In one or more embodiments, the co-solvent is a polyol. In one or more
embodiments, the co-solvent is polyethylene glycol derivative, or glycerin. In one or
more embodiments, the oleaginous composition of the present invention includes a


mixture of at least one hydrophobic solvent and at least one co-solvent. The mixture of
at least one hydrophobic solvent and the at least one co-solvent may have a weight ratio
of about 1:8 to about 8:1. In one or more embodiments, a mixture of at least one
hydrophobic solvent and glycerin is used; and the mixture may have a weight ratio of
about 1:4to about 4:1, or about 1:2 to about 2:1.
[0019] According to one or more embodiments, the oleaginous composition includes
at least one solvent having a high solubilization capacity, termed herein a "potent
solvent". In the context of the present invention, a potent solvent is a solvent other than
mineral oil and solubilizes a specific active agent substantially better than a hydrocarbon
solvent such as mineral oil or petrolatum, for example, 5-fold better than mineral oil or
10-fold better than mineral oil.
[0020] In one or more embodiments, the oleaginous composition of the present
invention contains a potent solvent selected from the group consisting of a polyol,
polyethylene glycol, propylene glycol, hexylene glycol, butanediols and isomers thereof,
glycerol, benzyl alcohol, dimethyl solfoxide (DMSO), ethyl oleate, ethyl caprylate,
diisopropyl adipate, dimethylacetamide, N-methylpyrrolidone, N-hydroxyethylpyrrolidone,
polyvinylpyrrolidone, isosorbide derivatives, dimethyl isosorbide, glycofurol and
ethoxydiglycol (transcutol) and mixtures thereof in any proportion.
[0021] In one or more embodiments, the oleaginous composition includes at least
one gelling agent selected from the group consisting of natural polymeric materials,
semi-synthetic polymeric materials, synthetic polymeric materials, inorganic gelling
agents and mixtures thereof. Yet, in additional embodiments, a gelling agent is not
essential.
[0022] The oleaginous composition of the present invention upon extrusion from a
pressured container has a specific gravity of about 0.02 gr/ml to about 0.5 gr/mL, and is
useful for treating, alleviating or preventing a dermatological or mucosal disorder.
[0023] According to a further aspect of the present invention, an oleaginous water-in-
oil emulsion is provided. The emulsion can be essentially free of short chain alcohols.
The emulsion includes:
a. at least one solvent selected from the group consisting of a hydrophobic
solvent, a co-solvent and an emollient at a concentration of about 30% to about 96.5%
by weight;
b. water;
c. at least one non-ionic lipophilic surface acting agent having an HLB value of


about 3 to about 10 at a concentration of about 0.1 % to less than about 10% by weight;
d. optionally, at least one gelling agent at a concentration of about 0.1 % to about
5% by weight.
e. at least one active agent at a therapeutically effective concentration; and
f. at least one liquefied or compressed gas propellant at a concentration of about
3% to about 25% by weight of the total composition.
[0024] In one or more embodiments, the oleaginous water-in-oil emulsion contains
less than about 5% of a short chain alcohol having up to 5 carbon atoms in its carbon
chain skeleton. In another embodiment the oleaginous composition further includes a
foam adjuvant.
[0025] In one or more embodiments, the oleaginous water-in-oil emulsion contains a
hydrophobic solvent and water at a weight ratio of about 1:3 to about 6:1.
[0026] In one or more embodiments, the oleaginous water-in-oil emulsion contains a
hydrophobic solvent having solubility in distilled water at ambient temperature of less
than about one gram per 100 ml. The hydrophobic solvent may be selected from mineral
oil, MCT oil, triglyceride oil, silicone oil, a polyunsaturated oil, an unsaturated oil and an
essential oil.
[0027] The oleaginous water-in-oil emulsion may include a potent solvent selected
from the group consisting of a hydrophobic solvent other than mineral oil, a co-solvent
and an emollient, wherein the potent solvent solubilizes the active agent substantially
better than mineral oil solubilizes the active agent, e.g at least 5-fold better or at least 10-
fold better than, mineral oil solubilizes the active agent.
[0028] In one or more embodiments, the oleaginous water-in-oil emulsion contains a
surface-active agent having an HLB value in the range of about 3 to about 10, for
promoting the formation of a water-in-oil emulsion.
[0029] In one or more embodiments, the oleaginous water-in-oil emulsions contains
at least one gelling agent selected from the group consisting of natural polymeric
materials, semi-synthetic polymeric materials, synthetic polymeric materials, inorganic
gelling agents and mixtures thereof. Yet, in additional embodiments, a gelling agent is
not essential.
[0030] The active agent can be a therapeutic agent or a cosmetic agent. The
therapeutic agent is selected for the treatment or prophylaxis of a disorder of the skin,
mucosal membrane, ear channel, vagina, penile urethra and rectum. In one
embodiment therapeutic agent is selected from the group consisting of an anti-infective,


an antibiotic, an antibacterial agent, an antifungal agent, an antiviral agent, an
antiparasitic agent, an antiinflammatory agent, an anesthetic, an analgesic, an
antiallergic agent, a corticosteroid, a retinoid, an antiproliferative agent, an anticancer
agent, a photodynamic therapy agent, a lubricating agent and mixtures thereof.
[0031] Alternatively, the active agent is an inorganic solid matter, preferably a metal
oxide, more preferably titanium oxide and zinc oxide.
[0032] The active agent can also be a cosmetic agent such as a retinoid, an anti-
wrinkle agent, a radical scavenger, a self-tanning agent, a skin whitening agent a skin
protective agent, an anti-cellulite agent, a massaging oil and an anti-wart agent.
[0033] In another aspect, the present invention provides a method of treating,
alleviating or preventing a dermatological or mucosal disease or disorder by
administering topically to a subject having the disease or disorder a therapeutically
effective amount of the oleaginous compositions or the oleaginous water-in-oil emulsions
of the present invention.
[0034] In yet another aspect, the present invention also provides a method of
designing a foamable composition, containing at least one active agent that is
substantially insoluble in a hydrocarbon solvent including mineral oil. The method
includes selecting at least one active agent, and identifying a solvent that solubilizes the
active agent substantially better than mineral oil solubilizes the active agent. The
method may further include the step of adjusting the type and concentration of surface
active agent and gelling agent to provide a foamable composition.
[0035] In one or more embodiments, the potent solvent solubilizes the active agent
5-fold better or even 10-fold better than mineral oil solubilizes the active agent.
DETAILED DESCRIPTION OF THE INVENTION
[0036] Despite the commonly known fact that hydrophobic solvents, and oils in
particular, are difficult to formulate into foam-producing products and that addition of
conventional hydrophobic solvents interferes with the foam forming ability of the surface
active agent, the present invention has surprisingly discovered stable oleaginous foam
compositions. The oleaginous compositions may include at least one active agent for
dermal, transdermal and mucosal delivery. The oleaginous compositions are dispensed
as a foam providing a stable product that is pleasant and easy to use for high patient and
consumer compliance. The at least one active agent may be a therapeutically active
agent or a cosmetic agent.




[0037] The term "oleaginous" is defined as "having the nature or qualities of oil". The
terms "oleaginous composition", "oleaginous foam", "oleaginous emulsion" and
"oleaginous foamable composition," etc. as used herein interchangeably refer to a
composition that has the organoleptic character of an oily substance, i.e., oily feeling,
when topically administered to a body area, such as the skin or mucosal tissue.
Materials and properties for the oleaginous compositions and emulsions are described.
Although the description that follows may refer to an oleaginous composition, it is
understood that the materials are also suitable for use in an oleaginous emulsion, unless
otherwise stated.
[0038] Surprisingly, the oleaginous compositions of the present invention require low
surface active agent concentrations, e.g., less than 10% by weight and often much less,
thus minimizing both undesirable irritation and costly raw material usage. The foamable
compositions are light weight, have low density, spread easily and comfortably over large
body area, and are thus, very convenient to use and economical.
[0039] The oleaginous compositions of the present invention include at least one
solvent selected from the group consisting of a hydrophobic solvent, a co-solvent, an
emollient and mixtures thereof, which provides a refatting and skin soothing effect. In
one or more embodiments, the composition comprises at least 30% of said at least one
solvent. In one or more embodiments, the composition comprises at least 50% of said at
least one solvent. In one or more embodiments, the composition comprises at least 65%
of said at least one solvent. The selected solvents allow the inclusion of oil-soluble
active agents in the formulation. In one or more embodiments, the solvents provide
synergistic benefits in combination with the active agent. The compositions may
comprise at least one oil soluble active agent.
[0040] In one or more embodiments, the compositions require only low
concentrations of a foaming agent in order to generate a stable foam. The reduced
surface active agent requirement is advantageous since surface active agents are known
to be irritating when in contact with the skin at elevated concentrations.
[0041] The foamable compositions are easily spreadable, allowing treatment of large
areas such as the arms, back, trunk, legs and the breast. Furthermore, due to enhanced
flow properties, they spread effectively into folds and wrinkles and absorb into the skin,
providing uniform distribution of the active agent without the need of extensive rubbing
thus providing an attractive means for the treatment of large body areas. The foamable
compositions may be further used for the treatment of body cavities, such as the vagina,
7


penile urethra, rectum and the ear channel due to their expansion properties. In one or
more embodiments the foamable compositions may be further used for transdermal
delivery of drugs.
Glass A foam composition
[0042] According to one aspect the present invention provides an oleaginous foam
composition for topical application including:
at least one solvent selected from the group consisting of a hydrophobic
solvent, a co-solvent, an emollient and mixtures thereof, at a concentration of about 70%
to about 96.5% by weight,
at least a non-ionic surface active agent at a concentration of about 0.1% to
about 10% by weight and, optionally, having an HLB value of about 9 or less;
optionally, at least one gelling agent at a concentration of about 0.1% to about
5% by weight;
at least one active agent at a therapeutically effective concentration; and
a propellant at a concentration of about 3% to about 25% by weight of the
total composition.
[0043] The balance of the composition contains water and additional optional
components. The content of the foam composition is presented herein as concentration
(percent by weight, % w/w). The foam composition can be a homogeneous mixture or
an emulsion.
[0044] Such a composition is placed in a pressurized aerosol container and, upon
release from the container, creates a novel therapeutically-beneficial foam product.
[0045] Low water content provides high skin and body tissue lubrication, refatting,
regulating residence of an active ingredient in the skin effects and effective skin
absorption of a active agents. It is also helps to avoid degradation of water sensitive
active agents.
[0046] Thus, in one or more embodiments, the oleaginous composition includes
water at a concentration of about 30% or less, or at a concentration less than about 20%,
or at a concentration less than about 10% by weight.
[0047] The oleaginous composition is optionally substantially free of short chain
alcohols, i.e. comprises less than about 5% by weight of a short chain alcohol having 5
or less carbon atom in its skeleton, and may further comprise a foam adjuvant.
[0048] According to one embodiment, the oleaginous composition contains a solvent
selected from the group consisting of a hydrophobic solvent and an emollient and at


least one co-solvent. According to one embodiment, the co-solvent is an organic solvent
other than a short chain alcohol, that dissolves in water. Non-limiting examples of such
co-solvents include polyols, propylene glycol, glycerol, and other polyhydroxy solvents
(polybls). Preferably, the composition includes glycerol as co-solvent. In one
embodiment, the composition includes a hydrophobic solvent component and a co-
solvent at a weight ratio in the range of about 4:1 and about 1:4, or about 2:1 to 1:2. In a
further embodiment of the present invention, the co-solvent constitutes a continuous
phase of the emulsion and a minor portion of water is included in the co-solvent phase.
[0049] Such a composition is placed in an aerosol container and, upon release from
the aerosol container, creates a therapeutically-beneficial foam product.
Class B foam composition:
[0050] According to another aspect the present invention provides an oleaginous
foam composition may be a water-in-oil emulsion, i.e., an emulsion having one phase
including at least one hydrophobic component (oil phase) and one phase which includes
water. Due to the fact that the continuous phase of the emulsion is the oil phase, the
composition provides an oily feeling, regulating residence of an active ingredient in the
skin properties and protective effects. Notably, while it is known that a composition with
a continuous oil phase is unlikely to form foam without high amounts of surface active
agents, the oleaginous water-in-oil emulsion surprisingly forms a stable foam with low
density. In one or more embodiments, there is an overlap between the compositions of
Class A and Class B, the distinction being that Class B compositions are formed as
water-in-oil emulsions.
[0051] According to one embodiment, the water-in-oil emulsion composition
contains:
at least one solvent selected from the group consisting of a hydrophobic
solvent, a co-solvent, an emollient and mixtures thereof, at a concentration of about 30%
to about 96% by weight,
water at a concentration of 1% to about 70% by weight;
at least one non-ionic lipophilic surface active agent.for example, having an HLB
value of about 3 to about 10, more preferably about 3.5 to about 9 at a concentration of
about 0.1% to about 10% by weight, or between about 0.1% and about 5% by weight, or
even between about 0.1% and about 2% by weight;



optionally, at least one gelling agent at a concentration of about 0.1 % to about
5% by weight;
at least one active agent at a therapeutically effective concentration; and
a propellant at a concentration of about 3% to about 25% by weight of the
total composition, in an aerosol container.
[0052] According to a further embodiment, the ratio between the oil phase and water
is between about 1:3 and about 6:1.
[0053] An oleaginous foam emulsion is a composition having at least one solvent
selected from the group consisting of a hydrophobic solvent, a co-solvent, an emollient
and mixtures thereof in the continuous phase of the composition and is characterized by
an oily feeling upon application to a body surface.
[0054] An oleaginous composition or emulsion may provide an enhanced regulating
residence of an active ingredient in the skin effect, which may in turn control the drug
residence time and skin penetration of an active agent. Furthermore, oleaginous
compositions and emulsions provide moisturizing effects, refatting effects, protective
effects and lubrication, all of which contribute to the treatment of dermatological
disorders. Thus, a composition of this nature, comprising an oleaginous vehicle and an
active agent is expected to provide a synergistic therapeutic effect.
Solvents
[0055] The solvent of the composition of the present invention is selected from the
group consisting of a hydrophobic solvent, an emollient, a silicone oil, a co-solvent, and a
mixture thereof. The solvent occupies at least the continuous phase; however, it may
also partition into the discontinuous phase in those instances when the composition is an
emulsion.
Hydrophobic solvent
[0056] A "hydrophobic solvent" as used herein includes but is not limited to a
material having solubility in distilled water at ambient temperature of less than about 1
gm per 100 mL, or less than about 0.5 gm per 100 mL, or even less than about 0.1 gm
per 100 mL. It is liquid at ambient temperature. The identification of a hydrophobic
solvent by its solubility in water is not intended to characterize the solubilization
capabilities of the solvent for any specific active agent or any other component of the
foamable composition. Rather, such information is provided to aid in the identification of


materials suitable for use as a hydrophobic solvent in the foamable compositions
described herein.
[0057] In one embodiment, the solvent is a hydrophobic solvent such as mineral oil.
Mineral oil (Chemical Abstracts Service Registry number 8012-95-1) is a mixture of
aliphatic, naphthalenic, and aromatic liquid hydrocarbons that derive from petroleum.
They are typically liquid; their viscosity is in the range of between about 35 CST and
about 100 CST (at 40°C); and their pour point (the lowest temperature at which an oil
can be handled without excessive amounts of wax crystals forming so preventing flow) is
below 0°C. By contrast, white petrolatum, also termed "Vaseline", is disadvantageous,
due to the waxy nature and semi-solid texture of petrolatum. It is known to leave a waxy
and sticky feeling after application and occasionally stain cloths. Thus, white petrolatum
as well as other wax-like, semi-solid compounds are undesirable as a hydrophobic
solvent according to the present invention.
[0058] According to one embodiment, the oleaginous foam composition of the
present invention includes a hydrophobic solvent selected from mineral oil, a triglyceride
oil, an ester of a fatty acid, an ester of a dicarboxylic acid, silicone oil, a polyunsaturated
oil, an unsaturated oil and an essential oil.
[0059] According to one embodiment, hydrophobic solvents are liquid oils originating
from vegetable, marine or animal sources. The hydrophobic solvent may be selected
from the group consisting of a saturated or an unsaturated oil. Preferably, the
unsaturated oil is selected from the group consisting of an olive oil, a com oil, a soybean
oil, a canola oil, a cottonseed oil, a coconut oil, a sesame oil, a sunflower oil, a borage
seed oil, an syzigium aromaticum oil, a hempseed oil, a herring oil, a cod-liver oil, a
salmon oil, a flaxseed oil, a wheat germ oil, an evening primrose oil and any mixtures
thereof, at any proportion.
[0060] One class of hydrophobic solvents includes, but is not limited to,
polyunsaturated oils, containing omega-3 and omega-6 fatty acids, which are know to
possess therapeutic properties through different modes of action. Examples of such
polyunsaturated fatty acids are linoleic and linolenic acid, gamma-linoleic acid (GLA),
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Thus, in one
embodiment of the present invention the hydrophobic solvent includes at least 6% of an
oil selected from omega-3 oil, omega-6 oil, and mixtures thereof.
[0061] Another class of hydrophobic solvents is the essential oils, which are
considered "therapeutic oils." Therapeutic oils contain active biologically occurring


molecules and, upon topical application, exert a therapeutic effect. Examples of such
oils are rosehip oil, which contain retinoids and is known to reduce acne and post-acne
sears, and tea tree oil, which possesses anti-microbial activity including antibacterial,
antifungal and antiviral properties. Other examples of essential oils are basil, camphor,
cardamom, carrot, citronella, clary sage, clove, cypress, frankincense, ginger, grapefruit,
hyssop, jasmine, lavender, lemon, mandarin, marjoram, myrrh, neroli, nutmeg, petitgrain,
sage, tangerine, vanilla, verbena, as well as any other therapeutically beneficial oil
known in the art of herbal medication.
Emollient
[0062] A further class of solvents is "emollients" that have a softening, refatting, or
soothing effect, especially when applied to body areas, such as the skin and mucosal
surfaces. Emollients are not necessarily hydrophobic, nor are they necessarily
solubilizing of the active agent or other components of the foamable compositions
described herein. Without derogating the generality of this definition, examples of
suitable emollients for use include hexyleheglycol, propylene glycol, isostearic acid
derivatives, isopropyi palmitate, isopropyl isostearate, diisopropyl adipate, diisopropyl
dimerate, maleated soybean oil, octyl palmitate, cetyl lactate, cetyl ricinoleate, tocopheryl
acetate, acetylated lanolin alcohol, cetyl acetate, phenyl trimethicone, glyceryl oleate,
tocopheryl linoleate, wheat germ glycerides, arachidyl propionate, myristyl lactate, decyl
oleate, propylene glycol ricinoleate, isopropyl lanolate, pentaerythrityl tetrastearate,
neopentylglycol dicaprylate/dicaprate, isononyl isononanoate, isotridecyl isononanoate,
myristyl myristate, triisocetyl citrate, octyl dodecanol, sucrose esters of fatty acids, octyl
hydroxystearate and mixtures thereof. Examples of other suitable emollients may be
found in the Cosmetic Bench Reference, pp. 1.19-1.22 (1996).
Silicone oil
[0063] Silicone oils possess skin protective properties and readily facilitate regulating
residence of an active ingredient in the skin regulating residence of an active ingredient
in the skin regulating residence of an active ingredient in the skin. Silicone oil may be
either a volatile silicon oil or a non-volatile silicone oil. Water-soluble silicones, such as
dimethicone copolyol are not included in the definition of silicone oils (as hydrophobic
solvents) according to the present invention. In one embodiment, the hydrophobic
solvent includes at least 2% (w/w) silicone oil, or at least 5% (w/w) silicone oil.


[0064] Any mixture, in any proportion of hydrophobic solvents as listed herein can be
used.
Go-solvent
[0065] A "co-solvent", in the context of the present invention is an organic solvent,
other than a short chain alcohols, typically soluble in both water and oil. Examples of co-
solvents, according to the present invention include polyols, sulfoxides, oieates, lactam
compounds, esters, amides, alkanoic acids, and alkanols and admixtures thereof.
Exemplary polyols include glycerol (glycerin), propylene glycol, hexylene glycol,
diethylene glycol, propylene glycol n-alkanols, terpenes, di-terpenes, tri-terpenes, terpen-
ols, limonene, terpene-ol, 1-menthol, dioxolane, ethylene glycol, and other glycols.
Exemplary sulfoxides include dimethylsulfoxide (DMSO), dimethylformanide, methyl
dodecyl sulfoxide, and dimethylacetamide. Exemplary oieates include monooleates of
ethoxylated glycerides (with 8 to 10 ethylene oxide units) and triolein. Exemplary lactam
compounds include azone (T-dodecylazacycloheptan-2-one) and2-(n-nonyl)-1,3-
dioxolane. Exemplary esters includeisopropyl myristate/palmitate, ethyl acetate, butyl
acetate, methyl proprionate, capric/caprylic triglycerides, octylmyristate, and dodecyl-
myristate. Exemplary amides include acetamide. Other suitable co-solvents include
myristyl alcohol, lauryl alcohol, lauric acid, lauryl lactate ketones; various alkanoic acids
such as caprylic acid and alkanols, such as dialkylamino acetates.
[0066] According to one embodiment, the co-solvent is a polyethylene glycol (PEG)
or a PEG derivative, and mixtures thereof, that are flowable at ambient temperature,
including PEG200 (MW about 190-210 kD), PEG300 (MW about 285-315 kD), PEG400
(MW about 380-420 kD), PEG600 (MW about 570-630 kD) and higher MW PEGs such
as PEG 4000, PEG 6000 and PEG 10000 and mixtures thereof, provided, however, that
said PEG or mixture of PEGs is flowable at ambient temperature. By "flowable", as that
term implies, the polyethylene glycol may be viscous at ambient temperature. The PEG
or PEG mixture can have a viscosity of about 20,000cps at ambient, or less than about
10,000 cps at ambient.
[0067] In one or more embodiments, the solvent is a mixture (e.g., an emulsion) of a
hydrophobic solvent and glycerin, as described, for example, in US Pat. No.6,544,530 to
Friedman. The ratio of hydrophobic solvent to glycerin can range from about 1:4 to
about 4:1, and more preferably from about 1:2 to about 2:1.
[0068] In several cases, a given solvent can be defined as both emollient and co-
solvent. A co-solvent may also be a potent solvent for selected active agents.


Potent solvent
[0069] In one or more embodiments of the present invention, the foamable
composition includes a potent solvent, in addition to or in place of one of the hydrophobic
solvents, co-solvents and emollients of the composition. A potent solvent is a solvent
other than mineral oil that solubilizes a specific active agent substantially better than a
hydrocarbon solvent such as mineral oil or petrolatum. For example, a potent solvent
solubilizes the active agent 5 fold better than a hydrocarbon solvent; or even solubilizes
the active agent 10-fold better than a hydrocarbon solvent. The solubility of a given
active agent in the potent solvent relative to its respective solubility in mineral oil is
determined in the absence of the composition. That is, the potent solvent alone
solubilizes the active agent better than the the mineral oil alone. This is an independent
test, irrespective of the composition in which the potent solvent is incorporated.
[0070] In one or more embodiments of the present invention, the composition
includes at least one active agent in a therapeutically effective concentration and at least
one potent solvent in a sufficient amount to substantially solubilize the at least one active
agent in the composition. The term "substantially soluble" means that at least 95% of the
active agent has been solubilized, i.e., 5% or less of the active agent is present in a solid
state. In one or more embodiments, the concentration of the at least one potent solvent
is more than about 40% of the at least one solvent of the composition of the present
invention; or even more than about 60%.
[0071] Non-limiting examples of pairs of active agent and potent solvent include:
Betamethasone valerate/ glycofurol: Practically insoluble in mineral oil ( soluble more than 1 % in glycofurol.
Hydrocortisone butyrate/ glycofurol: Practically insoluble in mineral oil ( soluble more than 1% in glycofurol.
Metronidazole/dimethyl isosorbide: Practically insoluble in mineral oil ( soluble more than 1% in dimethyl isosorbide.
Ketoconazole/dimethyl isosorbide: Practically insoluble in mineral oil ( soluble more than 1% in glycofurol, propylene glycol and dimethyl isosorbide.
Mupirocin/various solvents: Practically insoluble in mineral oil ( more than 1% in glycofurol, hexylene glycol, dimethyl isosorbide, propylene glycol and
polyethylene glycol 400 (PEG 400).
Meloxicam, a nonsteroidal anti-inflammatory agent/propylene glycol: Practically
insoluble in mineral oil (





400:3.7 mg/mL.
Progesterone/PEG 400: Practically insoluble in mineral oil ( PEG 400:15:3 mg/mL
[0072] A non-limiting exemplary list of solvents that can be considered as potent
solvents includes polyols, polyethylene glycol (PEG), propylene glycol, hexylene glycol,
butanediols and isomers thereof, glycerol, benzyl alcohol, DMSO, ethyl oleate, ethyl
caprylate, diisopropyl adipate, dimethylacetamide, N-methylpyrrolidone, N-
hydroxyethylpyrrolidone, polyvinylpyrrolidone, isosorbide derivatives, such as dimethyl
isosorbide, glycofurol and ethoxydiglycol (transcutol) and mixtures thereof in any
proportion.
[0073] In another aspect, the present invention provides a method of designing a
stable oleaginous foamable composition by selecting at least one active agent and
identifying a solvent that solubilizes the active agent substantially better than mineral oil
or petrolatum, for example, solubilizes the active agent 5-fold better or even 10-fold
better than a hydrocarbon solvent such as mineral oil or petrolatum. The method may
further include adjusting the type and concentration of surface active agent and gelling
agent to provide a foamable composition.
[0074] The use of a potent solvent in a foam composition provides an improved
method of delivering poorly soluble therapeutic agents to a target area. It is known that
low drug solubility results in poor bioavailability, leading to decreased effectiveness of
treatment. Foam compositions of the present invention, for which the solvent includes a
potent solvent, increase the levels of the active agent in solution and thus, provide high
delivery and improved therapy.
[0075] Potent solvents, as defined herein, are usually liquid. Formulations
comprising potent solvents and active agents are generally disadvantageous as
therapeutics, since their usage involves unwanted dripping and inconvenient method of
application, resulting in inadequate dosing. The foams described herein are drip-free,
provide a superior vehicle for such active agents, and enable convenient usage and
accurate effective dosing.
[0076] The solvent of the present invention may include a mixture of the above
solvents selected from the group of hydrophobic solvents, silicone oils, emollients co-
solvents and potent solvents in any proportion.
Surface-active agents




[0077] Surface-active agents may include an agent useful in forming an emulsion
and/or evolving a foam. A surface active agenfs hydrophilic/lipophilic balance (HLB)
describes the surface active agenfs affinity towards water or oil. The HLB scale ranges
from about 1 (totally lipophilic) to 45 (totally hydrophlic) and in the case of non-ionic
surface active agents from 1 to 20 (totally hydrophlic), with 10 representing an equal
balance of of both hydrophilic and lipophilic characteristics. Lipophilic emulsifiers from
water-in-oil (w/o) emulsions, hydrophilic surface active agents form oil-in-water (o/w)
emulsions. The HLB of a blend of two emulsifiers equals the weight fraction of emulsifier
A times its HLB value, plus the weight fraction of emulsifier B times its HLB value (e.g., a
weighted average).
[0078] Without wishing to be bound by any particular theory or mode of operation,
hydrophilic surface active agents produce oil-in-water (o/w) microemulsions, whereas
lipophilic surface active agents are used to promote emulsification of the aqueous phase
into the oil phase.
[0079] The oleaginous composition of the present invention according to one or
more embodiments includes at least one surface active agent or surface active agent,
which is intended to both stabilize the formulation and to evolve an acceptable foam.
[0080] A composition having a low concentration of an ionic surface active agent is
desirable in terms of safety, since high concentrations of surface active agents are
known to evolve skin and mucosal membrane irritation. Unlike certain foamable
oleaginous compositions of the art, the total surface active agent employed to obtain
foam that is stable, of low specific gravity and has a fine bubble structure is relatively
low. Low surface active agent levels, particularly of ionic surface active agents, are
helpful in minimizing skin irritations. Total surface active agent may be in the range of
about 0.1% to less than about 10% of the foamable composition, and is typically less
than about 5%, or even less than about 2%. Yet, in one or more embodiments, when the
composition comprises a liquid polar polyol or polyol mixture, such as polyethylene
glycol, a foam can be produced even without a surface active agent.
[0081] According to one or more embodiments, the surface active agent is selected
from hydrophilic, hydrophobic, and a mixture of hydrophilic and hydrophobic surface
active agents. As is well known in the art, the terms "hydrophilic" and "hydrophobic" are
relative terms. A combination of surface-active agents is possible.
[0082] According to one or more embodiments, suitable surface active agents for
formation of a water-in-oil emulsion have an HLB value of no greater than 10, and for



example from about 3 to about 9. Thus, the composition may include a single surface-
active agent having an HLB value between 3 and 9, or a mixture of surface-active agents
having a weighted average of their HLB values between 3 and 9.
[0083] Suitable water-in-oil surface active agents 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. In
conjunction with the oil component being a silicone oil, the preferred emulsifiers are
hydroxylated derivatives of polymeric silicones and alkylated derivatives thereof.
[0084] According to one or more embodiments the present invention, the
composition comprises at least one non-ionic surface active agent. In one or more
embodiments, the composition includes at least one non-ionic surface active agent and
at least one ionic surface active agent selected from the group consisting of an anionic
surface active agent, a cationic surface active agent and a zwitterionic surface active
agent, at a weight ratio of between about 1:1 and about 20:0.1, or preferably at a weight
ratio of about 4:0.1 to about 20:0.1.
[0085] The choice of specific surface active agents should be made keeping in mind
the particular hydrophobic therapeutic agent to be used in the composition, and the
range of polarity appropriate for the chosen therapeutic agent. With these general
principles in mind, a very broad range of surface active agents is suitable.
[0086] Additional non-limiting examples of possible surface active agents include
polysorbates, such as polyoxyethylene (20) sorbitan monostearate (Tween 60) and
polyoxyethylene (20) sorbitan monooleate (Tween 80); Polyoxyethylene (POE) fatty acid
esters, such as Myrj 45, Myrj 49 and Myrj 59; poly(oxyethylene) alkylyl ethers, such as
poly(oxyethylene) cetyl ether, poly(oxyethylene) palmityl ether, polyethylene oxide
hexadecyl ether, polyethylene glycol cetyl ether, brij 38, brij 52, brij 56 and brij W1;
sucrose esters, partial esters of sorbitol and sorbitol anhydrides, such as sorbitan
monolaurate and sorbitan monolaurate; fatty alcohols or acids, mono or diglycerides,
isoceteth-20, sodium methyl cocoyl taurate, sodium methyl oleoyl taurate, sodium lauryl
sulfate, triethanolamine lauryl sulfate and betaines, provided that, in the case of a single
surface active agent, the HLB value is between 3 and 9; and in the case of a mixture of
surface-active agents, the weighted average of their HLB values is between 3 and 9.


[0087] In one or more embodiments, the at least one surface active agent is a
phospholipid. In a one or more embodiments, the phospholipid is phosphatidylcholine or
1,2-diacyl-sn-glycerol-3-phosphorylcholine, also termed "lecithin", which is a naturally
occuring phospholipid which possesses surface active agent properties. Lecithin is the
most abundant lipid in the membranes of biological tissues and as such, is considered a
non-irritant. Lethicin is a phospholipid composition very similar in composition to that of
human skin. For this reason, it is possible to use lethicin as an emulsif ier or a surfact-
active agent at levels about 10% by weight. In one or more embodiments, the surface-
active agent includes lethicin up to about 10% by weight and the total surfact-active
agent (when a mixture of agents is used) can be up to 15% by weight.
[0088] A composition having a low concentration of an ionic surface active agent, or
even no ionic surface active agent, is desirable in terms of safety, since high
concentrations of surface active agents are known to evolve skin irritation.
Gelling agents
[0089] The composition according to one or more embodiments of the present
invention include at least one gelling agent at a concentration of about 0.1% to about
5%. The at least one gelling agent is selected from the group consisting of a natural
polymeric material, a semi-synthetic polymeric material, a synthetic polymeric material,
an inorganic gelling agent and mixtures thereof. Yet, in one or more embodiments, a
foam with favorable properties can be produced even without a gelling agent.
[0090] Exemplary gelling agents that can be used in accordance with one or more
embodiments of the present invention include for example, but are not limited to,
naturally-occurring polymeric materials such as, locust bean gum, sodium alginate,
sodium caseinate, egg albumin, gelatin agar, carrageenin gum sodium alginate, xanthan
gum, quince seed extract, tragacanth gum, starch, chemically modified starches and the
like, semi-synthetic polymeric materials such as cellulose ethers (e.g. hydroxyethyl
cellulose, methyl cellulose, carboxymethyl cellulose, hydroxy propylmethyl cellulose),
polyvinylpyrrolidone, polyvinylalcohol, guar gum, hydroxypropyl guar gum, soluble
starch, cationic celluloses, cationic guars and the like and synthetic polymeric materials
such as carboxyvinyl polymers, polyvinylpyrrolidone, polyvinyl alcohol polyacrylic acid
polymers, polymethacrylic acid polymers, polyvinyl acetate polymers, polyvinyl chloride
polymers, polyvinylidene chloride polymers and the like. Optionally, mixtures of the
above compounds are contemplated.



[0091 ] It has been surprisingly discovered that certain gelling agents provide foam
compositions that produce foams with high foam stability and an appealing organoleptic
feel, even in the absence of foam stabilizing agents such as fatty acids and fatty
alcohols. The gelling agent is selected from the class of amphiphilic. copolymers.
Amphiphilic copolymers include polymers having hydrophobic groups and hydrophilic
groups or regions. These materials are referred to alternatively as "polymeric
surfactants" because the hydrophilic and hydrophobic regions of the polymers serve to
interact with and stabilize hydrophilic and lipophilic components, respectively, of a
composition. The copolymer may be a random copolymer, a block copolymer of a graft
or comb copolymer. Exemplary amphiphilic copolymers include include di-, tri- or multi-
block copolymer or graft copolymer of a biodegradable polymer.
[0092] The polymeric surfactant may be an acrylate copolymer, in which hydrophobic
moieties are chemically linked to hydrophilic polymer or hydrophilic moieties are attached
to hydrophobic polymers to produce amphiphilic surface active and surface stabilizing
agent. By way of example, suitable polymeric surfactants include cross linked
copolymers of acrylic acid and a hydrophobic comonomer, such as Pemulen TFM and
Pemulen TR-2, ETD 2020 and Carbopol 1382 (all, Acrylates/C10-30 alkyl acrylate
crosspolymer), Natrosol CS Plus 330 and 430 and Polysurf 67 ( all, cetyl hydroxyethyl
cellulose), Aculyn 22 (acrylates /steareth-20 methacrylate copolymer), Aculyn 25
(acrylates/ laureth-25 methacrylate copolymer), Aculyn 28 (acrylates/beheneth-25
methacrylate copolymer), Aculyn 46 (PEG-150/stearyl alcohol/SMDI copolymer),
Stabylen 30 (acrylates/vinyl isodecanoate), Structure 2001 (acrylates/steareth-20
itaconate copolymer), Structure 3001 (acrylates/ceteth-20 itaconate copolymer) and
Structure Plus (acrylates/aminoacrylates/C10-30 alkyl PEG 20 itaconate copolymer),
where PEG is polyethylene glycol, PPG is polypropylene glycol.
[0093] Other exemplary amphiphilic copolymers include silicone polymers such as
amphiphilic silicone polyols or copolyol, for example cetyl dimethicon copolyol and
dimethicone copolyol PPG-3 oleyl ether, acetylated starch derivatives, amphiphilic
modified starches, and amphiphilic block copolymers of ethylene oxide, propylene oxide
and/or propylene glycol (also known as "poloxamer").
[0094] The gelling agent may include other types of gelling agents, in combination
with an amphiphilic copolymer. For example, naturally-occurring thickening agents may
be included. Exemplary polymeric materials include locust bean gum, sodium alginate,
sodium caseinate, egg albumin, gelatin agar, carrageenin gum sodium alginate, xanthan


gum, quince seed extract, tragacanth gum, starch, chemically modified starches and the
like, semi-synthetic polymeric materials such as cellulose ethers (e.g. hydroxyethyl
cellulose, methyl cellulose, carboxymethyl cellulose, hydroxy propylmethyl cellulose),
polyvinylpyrrolidone, polyvinylaleohol, guar gum, hydroxypropyl guar gum, soluble
starch, cationic celluloses, cationic guars and the like and synthetic polymeric materials
such as carboxyvinyl polymers, polyvinylpyrrolidone, polyvinyl alcohol polyacrylic acid
polymers, polymethacrylic acid polymers, polyvinyl acetate polymers, polyvinyl chloride
polymers, polyvinylidene chloride polymers and the like. Optionally, mixtures of the
above compounds are contemplated.
[0095] The amphiphilic copolymer may be selected from the group consisting of
Pemulen polymeric surfactants, acrylates/C10-30 alkyl acryl ate crosspolymer, cetyl
hydroxyethyl cellulose, acrylates /steareth-20 methacrylate copolymer, acrylates/ laureth-
25 methacrylate copolymer, acrylates /beheneth-25 methacrylate copolymer, PRG-
150/stearyf alcohol/SMDI copolymer, acrylates/vinyl isodecanoate, acrylates/steareth-20.
itaconate copolymer, acrylates/ceteth-20 itaconate copolymer and
acrylates/aminoacrylates/C10-30 alkyl PEG 20 itaconate copolymer, amphiphilic silicone
polymers, alkyl dimethicon copolyol, cetyl dimethicon copolyol, dimethicone copolyol
PPG-3 oleyl ether, acetylated starch derivatives, amphiphilic modified starches, and
amphiphilic block copolymers of ethylene oxide, propylene oxide and/or propylene glycol.
[0096] Further exemplary gelling agents include the acrylic acid/ethyl acrylate
copolymers and the carboxyvinyl polymers sold, for example, by the B.F. Goodrich
Company under the trademark of Carbopol® resins. These resins consist essentially of
a colloidal water-soluble polyaikenyl polyether crosslinked polymer of acrylic acid
crosslinked with from 0.75% to 2% of a crosslinking agent such as polyallyl sucrose or
polyallyl pentaerythritol. Examples include Carbopol® 934, Carbopol® 940, Carbopol®
950, 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 allyl groups for each sucrose molecule.
[0097] Yet, another group of gelling agents includes, but is not limited to, inorganic
gelling agents, such as silicone dioxide (fumed silica) including but not limited to
AEROSIL 200 (DEGUSSA).
[0098] The gelling agent is present in an amount in the range of about 0.1 % to about
5.0 wt% of the foamable composition. In one or more embodiments, it is typically less
than 1 wt% of the foamable composition.



[0099] The gelling agent is present in the foam carrier or composition in an amount
of about 0.1 to 5.0 wt% by weight. The gelling agent included in the foamable
composition can be less than 1 wt% by weight of the foamable oleaginous composition.
Foam adjuvants
[00100] The oleaginous composition of the present invention may optionally further
include at least one foam adjuvant. In one or more embodiments, foam adjuvants
include fatty alcohols having 15 or more carbons in their carbon chain, such as cetyl
alcohol and stearyl alcohol (or mixtures thereof). Other examples of fatty alcohols are
oleyl alcohol (C18, unsaturated), arachidyl alcohol (C20), behenyl alcohol (C22), 1-
triacontanol (C30), as well as alcohols with longer carbon chains (up to-C50). The
concentration of the fatty alcohol that is required to support the foam system is inversely
related to the length of its carbon chains. Fatty alcohols derived from beeswax including
a mixture of alcohols, a majority of which has at least 20 carbon atoms in their carbon
chain, are especially well suited as foam adjuvants according to the present invention.
[00101] Another class of foam adjuvants, according to one or more embodiments of
the present invention, includes fatty acids having 16 or more carbons in their carbon
chain, such as hexadecanoic acid (C16) stearic acid (C18), arachidic acid (C20), behenic
acid (C22), octacosanoic acid (C28), as well as fatty acids with longer carbon chains (up
to C50), or mixtures thereof.
[00102] Optionally, the carbon atom chain of the fatty alcohol or the fatty acid may
have at least one double bond. A further class of foam adjuvant according to the present
invention comprises a long chain fatty alcohol or fatty acid, wherein the carbon atom
chain is branched. In an additional preferred class of foam adjuvants, the carbon chain,
of said fatty acid is substituted with a hydroxyl group, such as 12-hydroxy stearic acid.
[00103] The foam adjuvant according to the present invention may comprise a mixture
of fatty alcohols, fatty acids and hydroxy fatty acids and derivatives thereof in any
proportion, providing that the total concentration is about 0.1% to about 10% (w/w)
preferably about 0.1% to about 5% (w/w) in one or more embodiments, the total
concentration is about 0.4% to about 2.5% (w/w) of the total composition.
[00104] A feature of fatty alcohols and fatty acids relevant to their use in the foamable
compositions according to one or more embodiments of the present invention is related
to their therapeutic properties per se. Long chain saturated and mono unsaturated fatty
alcohols, e.g., stearyl alcohol, erycyl alcohol, arachidyl alcohol and docosanol have been
reported to possess antiviral, anti infective, anti-proliferative and anti-inflammatory


properties (US Patent No. 4,874,794). Longer Chain fatty alcohols, e.g., tetracosanol,
hexacosanol, heptacosanol, octacosanol, triacontanol, etc. are also known for their
metabolism modifying properties and tissue energizing properties. Long chain fatty acids
have also been reported to possess anti-infective characteristics. Thus, the
pharmaceutical or cosmetic composition of the present invention including the optional
foam adjuvant provides an extra or added therapeutic benefit.
Water content
[00105] The creation of a foamable composition with low water content is not easy,
and usually requires very high concentrations of a foaming surface active agent system,
which may comprise a high proportion of ionic surface active agents. However, ionic
surface active agents are known to be skin irritants in a concentration-dependent
manner, and thus, their use in the treatment of sensitive skin and other body tissues is
very limited. Surprisingly, the oleaginous compositions of the present invention have a
low water content, and yet require very low concentration of surface active agents, which
are primarily non-ionic.
Substantially alcohol free
[00106] Short chain alcohols, having up to 5 carbon atoms in their carbon chain
skeleton, such as ethanol, propanol, isopropanol, butanol, iso-butanol, t-butanol and
pentanol are considered less desirable solvents or co-solvents due to their skin-irritating
effect. Thus, the composition of the present invention is substantially alcohol-free have
less than about 5% final concentration of short chain alcoholss, or less than 2%, or even
less than 1%.
Optional Ingredients
[00107] The pharmaceutical or cosmetic composition of the present invention
optionally includes a variety of therapeutic or cosmetic ingredients, which are added in
order to fine-tune the consistency of the formulation, protect the formulation components
from degradation and oxidation and bestow their cosmetic acceptability. Such an
excipient is preferably selected from the group consisting of a diglyceride, a triglyceride,
a stabilizing agent, an antioxidant, glycerol, a flavoring, a colorant agent an odorant
agent and any other formulation component known in the art of pharmaceutical and
cosmetic formulary. The pharmaceutical or cosmetic composition is very easy to use.
When applied onto the afflicted body surface of humans or animals, it is in a foam state,
allowing free application without drip or spillage. Upon further application of a


mechanical force, e.g., by rubbing the composition onto the body surface, it freely
spreads on the surface and is rapidly absorbed.
Active agents
[00108] It is to be understood that the active agents useful herein can in some
instances provide more than one benefit or operate via more than one mode of action.
Therefore, classifications herein are made for the sake of convenience and are not
intended to limit the active agent to that particular application or applications listed.
[00109] The foam composition is useful and advantageous for the treatment of skin
disorders and for skin care and cosmetic care. The addition of an oil having refatting,
protective and moisture-retaining properties in a spreadable foam form can substitute for
currently available dermatological and cosmetic creams, lotions, gels, etc.
[00110] In one or more embodiments of the present invention, the foam includes an
active agent directed to the treatment of a medical disorder or a cosmetic disorder. The
active agent can be categorized by the benefit it provides or by its postulated mode of
action. The active agents can in some instances provide more than one benefit or
operate via more than one mode of action. Therefore, classifications are made for the
sake of convenience and are not intended to limit the active to that particular application
or applications listed. Furthermore, foam compositions, with or without further active
ingredients, are suitable for the application as "cosmeceutical" preparations.
[00111] The composition of the present invention includes at least one active agent
that provides therapeutic or cosmetic activity.
[00112] The composition of the present invention having at least one "active agent",
provides the following benefits:
favorable spreadability and absorption, compared to conventional ointment,
cream, lotion and the like; improved treatment convenience, leading to better
compliance;
enhanced delivery, leading to elevated bioavailability of the drug or cosmetic
active agent in the target organ, thereby improving treatment efficacy.
[00113] In the context of the present invention, pharmaceutical and cosmetic active
agents are included under the definition of at least one active agent. According to one
embodiment the at least one active agent may be a single agent or a combination of
agents that can be dissolved in the oleaginous carrier composition.
[00114] According to one embodiment, the at least one active agent is a hydrophobic
agent, having solubility in distilled water at ambient temperature of less than about 1 gm


per 100 mL, more preferable less than, about 0.5 gm per 100 mL, and most preferably
less than about 0.1 gm per 100 mL In another embodiment, the at least one active
agent is any therapeutic or cosmetic agent, providing that it is encapsulated in a
hydrophobic envelope.
[00115] In another embodiment, the at least one active agent is insoluble and thus,
incorporated in the foamable carrier of the present invention by suspension.
[00116] Non-limiting examples of active agents include antibiotic, antibacterial,
antifungal, antiviral, antiinflammatory, anesthetic, analgesic, antiallergic, corticosteroid,
retinoidretinoids, lubricating agents and antiproliferative medications and mixtures
thereof at any proportion. The concentration of said agents may be adopted to exert a
therapeutic effect on a disease when applied to an afflicted area.
[00117] A general non-limiting list of hydrophobic active agents include abacavir,
acebutolol, acrivastine, alatrofloxacin, albuterol, albendazole, alprazolam, alprenolol,
amantadine, amiloride, aminoglutethimide, amiodarone, amitriptyline, amlodipine,
amodiaquine, amoxapine, amphetamine, amphotericin, amprenavir, amrinone,
amsacrine, astemizole, atenolol, atropine, azathioprine, azelastine, azithromycin,
baclofen, benethamine, benidipine, benzhexol, benznidazole, benztropine, biperiden,
bisacodyl, bisanthrene, bromazepam, bromocriptine, bromperidol, brompheniramine,
brotizolam, bupropion, butenafine, butoconazole, cambendazole, camptotiiecin,
carbinoxamine, cephadrine, cephalexin, cetrizine, cinnarizine, chlorambucil,
chlorpheniramine, chlorproguanil, chlordiazepoxide, chlorpromazine, chlorprothixene,
chloroquine, cimetidine, ciprofloxacin, cisapride, citalopram, clarithromycin, clemastine,
clemizole, clenbuterol, clofazimine, clomiphene, clonazepam, clopidogrel, clozapine,
clotiazepam, clotrimazole, codeine, cyclizine, cyproheptadine, dacarbazine, darodipine,
decoquinate, delavirdine, demeclocycline, dexamphetamine, dexchlorpheniramine,
dexfenfluramine, diamorphine, diazepam, diethylpropion, dihydrocodeine,
dihydroergotamine, diltiazem, dimenhydrinate, diphenhydramine, diphenoxylate,
diphenylimidazole, diphenylpyraline, dipyridamole, dirithromycin, disopyramide,
dolasetron, domperidone, donepezil, doxazosin, doxycycline, droperidol, econazole,
efavirenz, ellipticine, enalapril, enoxacin, enrofloxacin, eperisone, ephedrine, ergotamine,
erythromycin, ethambutol, ethionamide, ethopropazine, etoperidone, famotidine,
felodipine, fenbendazole, fenfluramine, fenoldopam, fentanyl, fexofenadine, flecainide,
flucytosine, flunarizine, flunitrazepam, fluopromazine, fluoxetine, fluphenthixol,
fluphenthixol decanoate, fluphenazine, fluphenazine decanoate, flurazepam,


flurithrbmycin, frovatriptan, gabapentin, granisetron, grepafloxacin, guanabenz,
halofantrine, hafoperidol, hyoscyamine, imipenem, indinavir, irinotecan, isoxazole,
isradipine, itraconazole, ketoconazole, ketotifen, labetalol, lamivudine, lanosprazole,
leflundmide, levofloxacin, lisinopril, lomefloxacin, loperamide, loratadine, lorazepam,
Idrrhetazepam, lysuride, mepacrine, maprotilinei mazindol, mebendazole, meclizine,
medazepam, mefloquine, melonicam, meptazinol, mercaptopurine, mesalamine,
mesoridazine, metformin, methadone, methaqualone, methylphenidate,
methylphenobarbital, methysergide, metoclopramide, metoprolol, metronidazole,
mianserin, miconazole, midazolam, miglitol, minoxidil, mitomycins, mitoxantrone,
molindone, montelukast, morphine, moxifloxacin, nadolol, nalbuphine, naratriptan,
natamycin, nefazoddne, nelfinavir, nevirapine, nicardipine, nicotine, nifedipine,
nimodipine, nimorazole, nisoldipine, nitrazepam, nitrofurazone, nizatidine, norfloxacin,
nortriptyline, nystatin, ofloxacin, olanzapine, omeprazole, ondansetron, omidazole,
oxamniquine, oxantel, oxatomide, oxazepam, oxfendazole, oxiconazole, oxprenolol,
oxybutynin, oxyphencyclimine, paroxetine, pentazocine, pentoxifylline, perchlorperazine,
perfloxacin, perphenazine, phenbenzamine, pheniramine, phenoxybenzamine,
phentermine, physostigmine, pimozide, pindolol, pizotifen, pramipexol, pranlukast,
praziquantel, prazosin, procarbazine, prochlorperazine, proguanil, propranolol,
pseudoephedrine, pyrantel, pyrimethamine, quetiapine, quinidine, quinine, raloxifene,
ranitidine, remifentanil, repaglinide, reserpine, ricobendazole, rifabutin, rifampin,
rifapentine, rimantadine, risperidone, ritonavir, rizatriptan, ropinirole, rosiglitazone,
roxaditine, roxithromycin, salbutamol, saquinavir, selegiline, sertraline, sibutramine,
sildenafil, sparfloxacin, spiramycins, stavudine, sulconazole, sulphasalazine, sulpiride,
sumatriptan, tacrine, tamoxifen, tamsulosin, temazepam, terazosin, terbinafine,
terbutaline, terconazole, terfenadine, tetramisole, thiabendazole, thioguanine,
thioridazine, tiagabine, ticlopidine, timolol, tinidazole, tioconazole, tirofiban, tizanidine,
tolterodine, topotecan, toremifene, tramadol, trazodone, triamterene, triazolam,
trifluoperazine, trimethoprim, trimipramine, tromethamine, tropicamide, trovafloxacin,
vancomycin, venlafaxine, vigabatrin, vinblastine, vincristine, vinorelbine, vitamin K5,
vitamin K6, vitamin K7, zafirlukast, zolmitriptan, Zolpidem, zopiclone, acetazolamide,
acetohexamide, acrivastine, alatrofloxacin, albuterol, alclofenac, aloxiprin, alprostadil,
amodiaquine, amphotericin, amylobarbital, aspirin, atorvastatin, atovaquone, baclofen,
barbital, benazepril, bezafibrate, bromfenac, bumetanide, butobarbital, candesartan,
capsaicin, captopril, cefazolin, celecoxib, cephadrine, cephalexin, cerivastatin, cetrizine,


chlorambucil; chlorothiazide, chlorpropamide, chlorthalidone,cinoxacin, ciprofloxacin,
clinofibrate, cloxacillin, cromoglicate, cromolyn, dantrolene, dichlorophen, diclofenac,
dicloxaeillin, dicumarol, difluntsah dimenhydrinate, divalproex, docusate, dronabinol,
enoximone, enalapril, enoxaein, enrofloxacin, epalrestat, eposartan, essential fatty acids,
estramustine, ethacrynic acid, ethotoin, etodolac, etoposide, fenbufen, fenoprofen,
fexofenadine, fluconazole, flurbiprofen, fluvastatin, fosinopril, fosphenytoin, fumagillin,
furosemide, gabapentin, gemfibrozil, gliclazide, glipizide, glybenclamide, glyburide,
glimepiride, grepafloxacin, ibufenac, ibuprofen, imipenem, indomethacin, irbesartan,
isotretinoin, ketoprofen, ketorolac, lamotrigine, levofloxacin, levothyroxine, lisinopril,
lornefloxacin, losartan, lovastatin, meelofenamic acid, mefenamic acid, mesalamine,
methotrexate, metolazone, montelukast, nalidixic acid, naproxen, natamycin, nimesulide,
nitrofurantoin, non-essential fatty acids, norfloxacin, nystatin, ofloxacin, oxacillin,
oxaprozin, oxyphenbutazone, penicillins, pentobarbital, perfloxacin, phenobarbital,
phenytoin, pioglitazone, piroxicam, pramipexol, pranlukast, pravastatin, probenecid,
probucol, propofol, propylthiouracil, quinapril, rabeprazole, repaglinide, rifampin,
rifapentine, sparfloxacin, sulfabenzamide, sulfacetamide, sulfadiazine, sulfadoxine,
sulfamerazine, sulfamethoxazole, sulfafurazole, sulfapyridine, sulfasalazine, sulindac,
sulphasalazine, sulthiame, telmisartan, teniposide, terbutaline, tetrahydrocannabinol,
tirofiban, tolazamide, tolbutamide, tolcapone, tolmetin, tretinoin, troglitazone,
trovafloxacin, undecenoic acid, ursodeoxycholic acid, valproic acid, valsartan,
vancomycin, verteporfin, vigabatrin, vitamin K-S (II), zafirlukast, and pharmaceutically
acceptable oil-soluble derivative and salts thereof.
Anti-infective Agents
[00118] Anti-infective agents include antibacterial, antifungal, antiviral, and anti-
parasitic agents.
Antibacterial agents
[00119] The term "antibacterial" as used herein shall include, but is not limited to, any
substance being destructive to or inhibiting the growth of bacteria or any substance
having the capacity to inhibit the growth of or to destroy bacteria and other
microorganisms, and are used in the treatment of infectious diseases.
[00120] One class of active agents is antibacterial agents. It is well known that
bacterial infections are involved in a variety of superficial and non-superficial disorders of
the skin and mucosal membranes. The antibacterial agent can be active against gram


positive and gram-negative bacteria, protozoa, aerobic bacteria and anaerobes. The
composition may include one or a combination of water soluble, oil soluble and
suspended antibacterial agents.
[00121] Specific oil-soluble species of macrolide antibiotics, such as erythromycin;
sulfonamide (in its base form), such as sulfanilamide, sulfadiazine and sulfacetamide;
mupirocin; tetracyclines, such as tetracycline and doxycycline; specific oil-soluble
species of synthetic and semi-synthesic penicillins and beta-lactams; cloramphenicol;
specific oil-soluble species of imidazoles; dicarboxylic acids, such as azelaic acid;
salicylates; peptide antibiotics; cyclic peptides, such as cyclosporine, tacrolimus,
pimecrolimus and sirolimus (rapamycin); and non-specific antibacterial agents such as
strong oxidants and free radical liberating compounds, bleaching agents, iodine
compounds and benzoyl peroxide.
[00122] Antibacterial compositions according to one or more
embodiments of the present invention may be used to treat infections of
the skin. An example of a very common skin infection is impetigo, a
bacterial disease caused by Staphylococcus aureus and beta-hemolytic
streptococci, which mainly afflicts children and infants. Various
antibacterial creams and ointments, such as mupirocin cream and
mupirocin ointment, have been utilized to treat impetigo, however,
treatment compliance is markedly impaired due to the fact that children
resist the extensive rubbing involved in cream and ointment treatment.
Foam, on the other hand, was found to be easily applied, without any
difficulty. It has been surprisingly discovered that a composition of
mupirocin and a vehicle containing PEG (as a potent solvent), a non-
ionic surface active agent and a gelling agent, where the non-ionic
surface-active agent at a concentration of 2% by weight and the total
amounts of surface-active agent is in the range of 2.5% by weight, and
propellant, afforded an excellent foam which was stable upon discharge
from the aerosol can and was easy to apply onto an afflicted area.
[00123] The composition according to one or more embodiments of the present
invention is particularly useful and beneficial in the prevention and treatment of
secondary infections, accompanying skin-structure damage, such as in cuts, wounds,
bums and ulcers. In all such cases, the present formulation is easy to use, being in foam
state upon application and absorbing into the skin instantly upon gentle application.


[00124] While being useful in the prevention and treatment of infections, the
antibacterial foam of the present invention is also applicable for decontaminating areas,
afflicted with bacterial warfare organisms, such as anthrax and smallpox.
Anti-fungal agents
[00125] Fungal infections are another object of treatment using the composition of the
present invention. Superficial fungal infection of the skin is one of the most common skin
diseases seen in general practice. Dermatophytosis is probably the most common
superficial fungal infection of the skin. It is caused by a group of fungi capable of
metabolizing the keratin of human epidermis, nails or hair. There are three genera of
dermatophytes causing dermatophytosis, i.e, microsporum, trichophyton and
epidermophyton.
[00126] Candidiasis is an infection caused by the yeast like fungus Candida albicans
or occasionally other species of Candida. Clinical syndromes of candidiasis include: (a)
oral candidiasis (thrush); (b) candidiasis of the skin and genital mucous membrane; and
(c) Candida paronychia, which inflicts the nail and nail bed; and (d) genital and vaginal
Candida, which inflict genitalia and the vagina.
[00127] Optionally, the pharmaceutical composition includes an antifungal drug, which
antifungal drug provides effecetive treatment against dermatophytes and Candida. The
antifungal drug can be selected from the group consisting of azoles, diazoles, triazoles,
miconazole, fluconazole, ketoconazole, clotrimazole, itraconazole griseofulvin, ciclopirox,
amorolfine, terbinafine, Amphotericin B, potassium iodide, flucytosine (5FC) and any
combination thereof at a therapeutically effective concentration.
[00128] The composition according to one or more embodiments of the present
invention is useful for example for the treatment and prevention of tinea corporis, tinea
pedis, tinea rubrum, tinea unguium, tinea cruris, tinea barbae and tinea versicolor, as
well as yeast infections, such as candidiasis, and candidal vaginitis.
Anti-viral agents
[00129] The composition according to one or more embodiments of the present
invention is particularly beneficial in treating and preventing viral infections. Cold sores
are caused by the herpes simplex Type 1 virus and are sometimes referred to as facial
herpes. Mollusca are small viral growths that appear singly or in groups on the face,
trunk, lower abdomen, pelvis, inner thighs, or penis. Shingles (herpes zoster), usually
occurs only once in a lifetime, appears as a rash (clusters of blisters with a red base).


Shingles is caused by the same virus responsible for chickenpox. Warts are a common,
benign skin tumor caused by viral infection.
[00130] Any known antiviral agent, in a therapeutically effective concentration, can be
incorporated in the foam composition according to one or more embodiments of the
present invention. The composition according to one or more embodiments of the
present invention includes a hydrophobic solvent for facilitating an enhanced rate of
penetration and better topical distribution of any of the above listed antiviral drugs.
Anti-inflammatory and anti-allergic agents
[00131] Yet, according to another embodiment of the present invention the active
agent is an antiinflammatory or anti-allergic agent. An anti-inflammatory agents or
antiallergic agent is selected from the group consisting of corticosteroids, non-steroidal
anti-inflammatory drugs (NSAIDs), antihistamines, immunosuppressant agents,
immunomodulators; and any combination thereof at a therapeutically effective
concentration.
[00132] The following table provides a summary of currently available corticosteroid
agent and their typical therapeutically effective concentration.

[00133] The concentrations of corticosteroid drugs, as presented in the above table
are provided herein only as example, and any therapeutically effective concentration of
such corticosteroids can be incorporated in the composition of the present invention.


[00134] Since corticosteroid drugs are typically hydrophobic, the composition
according to one or more embodiments of the present invention that includes a
hydrophobic solvent is suitable as a vehicle to facilitate better topical distribution,
improved occlusion and an enhanced rate of penetration of any of the above listed
drugs.
[00135] Corticosteroids are used for treating psoriasis and atopic dermatitis (AD),
common chronic inflammatory skin diseases, characterized by periodic flare-ups of
sharply defined red patches covered by scaly patches (in the case of psoriasis) and
inflamed skin in the case of AD.
[00136] It is envisaged that the composition according to one or more embodiments of
the present invention may provide a treatment for Psoriasis and AD.
[00137] Corticosteroid ointments, greasy preparations containing little or no water, are
typically used for treating psoriasis. Their main disadvantage is in their sticky feeling
subsisting, for extended periods subsequent to treatment being completed. Thereby
creating a latent inconvenience and possible discomfort to the treatment recipient. By
contrast, the oleaginous foam composition according to one or more embodiments of the
present invention, while possessing a considerable concentration of an oil (hydrophobic
solvent), spreads very easily throughout the afflicted area and absorbs into the skin
without leaving any untoward sensation or look.
[00138] Other non-limiting examples of inflammatory disorders, which can be
prevented or are treatable by the oleaginous compositions according to one or more
embodiments of the present invention, wherein the drug is a steroid are atopic dermatitis,
seborrhea, seborrheic dermatitis of the face and trunk, seborrheic blepharitis, contact
dermatitis, stasis dermatitis (gravitational eczema; varicose eczema), exfoliative
dermatitis (erythroderma), lichen simplex chronicus, pityriasis rosea and pemphigus.
[00139] Certain of the solvents that may be used in the preparation of the composition
according to one or more embodiments of the present invention include polyunsaturated
fatty acids, containing omega-3 and omega-6 fatty acids (e.g., linoleic and linolenic acid,
gamma-linoleic acid (GLA), eicosapentaenoic acid (EPA) and docosahexaenoic acid
(DHA), which are themselves beneficial in the treatment of psoriasis and other skin
inflammation conditions.
[00140] Nonsteroidal anti-inflammatory agents (NSAIDs) are useful against skin
abnormalities are may be added to the oleagionous foam compositions according to one
or more embodiments of the present invention. The variety of compounds encompassed


by NSAlDs is well-known to those skilled in the art. Specific non-steroidal anti-
inflammatory agents useful in the composition invention include, but are not limited to:
Oxicams, such as piroxieam, isoxicam, tenoxicam, sudoxieam;
Salicylates, such as salicylic acid ethyl salicylate, methyl salycilate, aspirin,
disalcid, benorylate, trilisate, safapryn, solprin, diflunisal, and fendosal;
Acetic acid derivatives, such as diclofenac, fenclofenac, indomethacin,
sulindac, tolmetin, isoxepac, furofenac, tiopinac, zidometacin, acematacin, fentiazac,
zomepirac, clindanac, oxepinac, felbinac, and ketorolac;
Fenamates, such as mefenamic, meclofenamic, flufenamic, niflumic, and
tolfenamic acids;
Propionic acid derivatives, such as ibuprofen, naproxen, benoxaprofen,
flurbiprofen, ketoprofen, fenoprofen, fenbufen, indopropfen, pirprofen, carprofen,
oxaprozin, pranoprofen, miroprofen, tioxaprofen, suprofen, alminoprofen, and tiaprofenic;
and
Pyrazoles, such as phenylbutazone, oxyphenbutazone, feprazone,
azapropazone, and trimethazone.
[00141] Any further steroidal and nonsteroidal compounds having the capacity to
prevent, alleviate the symptoms of, treat or cure inflammation processes are generally
included as possible anti-inflammatory agents, according to one or more embodiments of
the present invention.
[00142] Topical antihistaminic preparations currently available include 1 % and 2%
diphenhydramine, 5% doxepin, phrilamine maleate, chlorpheniramine and
tripelennamine, phenothiazines, promethazine hydrochloride and dimethindene maleate.
These active agents, as well as additional antihistamines, can also be incorporated in the
composition according to one or more embodiments of the present invention.
[00143] The therapeutic composition according to one or more embodiments of the
present invention optionally includes an anti-inflammatory and/or an antiallergic agent,
wherein said agent reduces the occurrence of pro-inflammatory cytokines or inhibits the
effect of pro-inflammatory cytokines.
[00144] It is envisaged that mixtures of any anti-inflammatory agents can be used, as
well as the dermatologicaliy acceptable salts, esters, amides, prodrugs and derivatives of
these agents.
[00145] Topical application of an oleaginous foamincluding a safe and effective dose
of an NSAID can be useful in the prevention and/or alleviation of the symptoms of


rheumatoid arthritis, osteoarthritis and pain. Topical NSAIDs can be also used in the
treatment of dermatological disorders, such as acne, rosacea, hair growth disorders,
actinic keratosis and certain skin cancer conditions.
[00146] Immunosuppressant agents, irflmunoregulating agents and
immunomodulators are chemically or biologically-derived agents that modify the immune
response or the functioning of the immune system (as by the stimulation of antibody
formation or the inhibition of white blood cell activity). Immunosuppressant agents and
immunomodulators include, among other options, cyclic peptides, such as cyclosporine,
tacrolimus, tresperimus, pimecrolimus, sirolimus (rapamycin), verolimus, laflunimus,
laquinimod and imiquimod. Such compounds, delivered in the foam of the present
invention, are especially advantageous in skin disorders such as psoriasis, eczema and
atopic dermatitis, where the large skin areas are to be treated. The oleaginous foam
compositions according to one or more embodiments of the present invention provide
excellent vehicles for such applications and are superior to conventional creams and
ointments.
Topical Anesthetics
[00147] Optionally, the compositions according to one or more embodiments of the
present invention include an effective amount of a topical anesthetic. The topical
anesthetic drug is selected from the group consisting of benzocaine, lidocaine,
bupivacaine, chiorprocaine, dibucaine, etidocaine, mepivacaine, tetracaine, dyclonine,
hexylcaine, procaine, cocaine, ketamine, pramoxine, phenol, and pharmaceutically
acceptable salts thereof. Mixtures of such anesthetic agents may be synergistically
beneficial.
[00148] The composition according to one or more embodiments of the present
invention includes any mixture of synergistically beneficial anesthetic agents.
Keratolytically active agents
[00149] The term "keratolytically active agent" as used herein, includes but is not
limited to a compound, which loosens and removes the stratum corneum of the skin, or
alters the structure of the keratin layers of skin.
[00150] Keratolytically active agents are used in the treatment of many dermatological
disorders, which involve dry skin, hyperkeratinization (such as psoriasis), skin itching
(such as xerosis), acne and rosacea.


[00151] Suitable keratolytically active agents include phenol and substituted phenolic
compounds. Such compounds are known to dissolve and loosen the intracellular matrix
of the hyperkeratinized tissue. As such, they are used in the treatment of dermatoiogical
disorders. Dihydroxy benzene and derivatives thereof have been recognized as potent
keratolytic agents. Resorcinol (m-dihydroxybenzene) and derivatives thereof are used
in anti-acne preparations. Hydroquinone (p-dihydroxybenzene), besides hydroquinone
anti-pigmentation properties, is also keratolytic. These compounds also exhibit
antiseptic properties. Cresols also possess bactericidal and keratolytic properties.
[00152] Vitamin A and Vitamin A derivatives, such as retinoic acid, isoretinoic acid,
retinol and retinal are another class of keratolytically active agents.
[00153] Another group of keratolytically active agents include alpha-hydroxy acids,
such as lactic acid and glycolic acid and their respective salts and derivatives; and beta-
hydroxy acids, such as salicylic acid (o-hydroxybenzoic acid) and salicylic acid salts and
pharmaceutically acceptable derivatives, which typically possess anti-inflammatory, as
well as keratolytic, activity.
[00154] Yet, another class of keratolytically active agents includes urea and urea
derivatives.
Retinoids
[00155] Another group of active agents includes, for example, retinol, retinal, all trans
retinoic acid and derivatives, isomers and analogs thereof, collectively termed "retinoids".
Etretinate, actiretin, isotretinoin, adapalene and tazarotene are further examples of
retinoid isomers and analogs. Compositions according to one or more embodiments of
the present invention including retinoids as the active agent can be used for the
treatment of acne, seborrhea, various dermatoses, inflammation of the skin, mucosal
membranes, vagina and the rectum, psoriasis, actinic keratosis and skin cancers, by
application onto the affected area.
Insecticide and Insect repellents agents
[00156] Insects, such as mosquitoes, biting flies, mites, gnats, fleas, chiggers,
punkies, sand flies, lice and ticks can be annoying and sometimes pose a serious risk to
human and animal health. In certain areas of the United States, mosquitoes can transmit
diseases like equine and St. Louis encephalitis. Biting flies can inflict a painful bite that
can persist for days, swell, and become infected. Ticks can transmit serious diseases
like Lyme disease and Rocky Mountain spotted fever.


[00157] There are several types of insect repellents to use when protecting people
and animals from flying or biting insects, spiders, ticks and mites. Examples of insect
repellants include, but are not limited to, DEET (N, N-diethyl-m-toluamide), dimethyl
phthalate, piperonyl butoxide and permethrin.
[00158] A further example of insect repellents includes the terpenoid compounds,
described in U.S. Patent No. 5,411,992, including:
Terpenoid-alcohol or terpene-ols are terpenoids which have at least one
hydroxyl group. Examples of terpene-ols include: C10H16O compounds, perillyl alcohol,
carveol, myrtenol, and cis-verbenol; C10H18O compounds, myrtanol, iso-pinocampheol,
dihydrocarveol, isopulegol, terpineol, terpinen-4-ol, nerol, geraniol, and linalool, and
C10H20O compounds, menthol, beta-citronellol, and dihydro-myrcenol.
Terpenoid-esters are terpenoidshaving at least one ester group that is the
product of the bonding of the hydroxyl group of a terpene-ol with an aliphatic carboxylic
acid that can contain functional groups such as the hydroxyl or amine on the aliphatic
chain. Examples of suitable aliphatic carboxylic acids include acetic acid, propionic acid,
lactic acid, and various amino acids. Examples of terpenoid-esters include: carvyl
acetate, carvyl propionate, and menthyl lactate.
[00159] Essential oils and perfumes also contain terpenoids. Non-limiting examples
of essential oils having a high content of terpene-ols and esters include bergamot (62%
terpenoids); sage (>50% terpenoids); styrax (>50% terpenoids); peppermint (>50%
terpenoids); and pine Siberian (75% terpenoids %). Terpenes, aldehydes and ketones
vary in their usefulness but as a general group have potential as insect-repellent.
[00160] The oleaginous foams according to one or more embodiments of the present
invention are particularly suitable for the effective uniform spreading of an insect
repellent agent onto large areas of the skin of humans and animals. The hydrophobic
solvent present in the foam composition helps retain the insect repellent on the skin
surface for an extended period of time.
[00161] Yet, in a further embodiment, the oleaginous foams according to one or more
embodiments of the present invention are suitable for delivery of insect-killing agents
(insecticides) to an afflicted external surface area of humans and animals. Thus, the
pharmaceutical or cosmetic composition according to one or more embodiment of the
present invention may include an insecticide, known in the art of parasitology. The
insecticide is selected from the group consisting of permethrin, hexachlorobenzene,
carbamate, naturally occurring pyrethroids, permethrin, allethrin, malathion, piperonyl


butoxide and any combination thereof at a therapeutically effective concentration. The
application of the composition is very convenient and it spreads easily, even over hairy
areas. The hydrophobic solvent present in the foam composition helps retain the
insecticide on the treated area for an extended period of time. Furthermore, the
presence ofa hydrophobic solvent in the foam of the present invention eases
mechanical removal of lice and nits with a comb.
Anti cancer agents
[00162] Anti cancer agents can also be used according to one or more embodiments
of the present invention in the treatment of skin malignant tumors, such as basal cell
carcinoma, squamous sell carcinoma, melanoma and Kaposi's sarcoma, as well as the
pre-cancerous condition actinic keratosis. In certain cases, topical cytotoxic and
antiproliferative drugs are used to treat or prevent such cancers, including 5-fluorouracil,
also called 5-FU. 5-FU, as well as any other anti-cancer agents, know in the art of
cancer medicine, can be incorporated in the foam at therapeutically effective levels.
[00163] A family of anticancer drugs, suitable for usage in the foam of the present
formulation includes anti-estrogens, such as tamoxifen.
Photodynamic therapy agents
[00164] The foam compositions according to one or more embodiments of the present
invention are also useful to deliver photo-sensitizing agents, known in the art of
photodynamic therapy. A photosensitizer is selected from the group consisting of
porphyrins, chlorins, bacteriochlorins, phthalocyanines, naphthalocyanines,
pheophorbides, purpurins, m-THPC, mono-L-aspartyl chlorin e6, bacteriochlorins,
phthalocyanines, benzoporphyrin derivatives and photosensitizer precursors, such as
aminolevulinic acid (ALA).
Active agents for burns, wounds, cuts and ulcers
[00165] The treatment of burns, wounds, cuts and ulcers.using the composition
according to one or more embodiments of the present invention is particularly
advantageous. The oleaginous foam compositions according to one or more
embodiments of the present invention may include a combination of anti-infective agents
(against bacteria, fungi and/or viruses), anti-inflammatory agents (steroidal and/or


NSAIDs) and pain relieving components. Upon application, the foam spreads easily,
covering the surface of the affected area, and without causing pain.
Cosmetic active agents
[00166] The oleaginous foams according to one or more embodiments of the present
invention are useful and advantageous for skin care and cosmetic care. The
combination of oil, having refatting, protective and moisture-retaining properties, in a
spreadable foam form, can be used to substitute currently used cosmetic skin care
creams, lotions, gels, etc. The foam compositions according to one or more
embodiments of the present invention, with or without further active ingredients, are
suitable for the further application as "eosmeceutical" preparation (cosmetic products
with therapeutic benefit), to treat "cosmetic" skin disorders, such as aging skin, wrinkles,
hyperpigmentation (melasma, chloasma, freckles, etc.), scaly skin and other skin
abnormalities.
[00167] The CTFA Cosmetic Ingredient Handbook describes a wide variety of non-
limiting cosmetic and pharmaceutical ingredients commonly used in the skin care
industry, which are suitable for use in the compositions of the present invention.
Examples of these ingredient classes include abrasives, absorbents, aesthetic
components such as fragrances, pigments, colorings/colorants, essential oils,
astringents, etc. (e.g., clove oil, menthol, camphor, eucalyptus oil, eugenol, menthyl
lactate, witch hazel distillate), anti-acne agents, anti-caking agents, antifoaming agents,
anti-microbial agents (e.g., iodopropyl butylcarbamate), antioxidants, binders, biological
additives, buffering agents, bulking agents, chelating agents, chemical additives,
colorants, cosmetic astringents, cosmetic biocides, denaturants, drug astringents,
external analgesics, film formers or materials, e.g., polymers, for aiding the film-forming
properties and substantivity of the composition (e.g., copolymer of eicosene and vinyl
pyrrolidone), opacifying agents, pH adjusters, propellants, reducing agents,
sequestrants, skin bleaching and lightening agents (e.g., hydroquinone, kojic acid,
ascorbic acid, magnesium ascorbyl phosphate, ascorbyl glucosamine), skin-conditioning
agents (e.g., humectants, including miscellaneous and regulating residence of an active
ingredient in the skin), skin soothing and/or healing agents (e.g., panthenol and
derivatives (e.g., ethyl panthenol), aloe vera, pantothenic acid and pantothenic acid
derivatives, allantoin, bisabolol, and dipotassium glycyrrhizinate), skin treating agents,
and vitamins and derivatives thereof.


[00168] In one embodiment, the active agent is a cosmetic agent selected from the
group consisting of: a retinoid, an anti-wrinkle agent, a radical scavenger, a self-tanning
agent, a skin whitening agent, a skin protective agent, an anti-cellulite agent, a
massaging oil and an anti-wart agent.
Anti-acne and anti-wrinkle active agents
[00169] An anti-acne agent is included in the composition according to one or more
embodiments of the present invention. The anti-acne agent is selected from the group
consisting of: resorcinol, sulfur, salicylic acid and salicylates, alpha-hydroxy acids,
nonsteroidal anti-inflammatory agents, benzoyl peroxide, retinoic acid, isoretinoic acid
and other retinoid compounds, adapalene, tazarotene, azelaic acid and azelaic acid
derivatives, antibiotic agents, such as erythromycin and clindamycin, zinc salts and
complexes, and combinations thereof, in a therapeutically effective concentration.
Certain anti-acne agents from this list are also useful in the treatment of other skin
disease, such as psoriasis, eczema and atopic dermatitis.
Anti-wrinkle active agents/anti-atrophy active agents and agents to treat dry and scaly
skin (xerosis and ichthyosis).
[00170] Optionally, the compositions according to one or more embodiments of the
present invention include a safe and effective amount of at least one anti-wrinkle
actives or anti-atrophy active. Exemplary anti-wrinkle/anti-atrophy active agents suitable
for use in the compositions according to one or more embodiments of the present
invention include sulfur-containing D and L amino acids and their derivatives and salts,
particularly the N-acetyl derivatives; thiols; hydroxy acids (e.g., alpha-hydroxy acids such
as lactic acid and glycolic acid and their derivatives and salts; or beta-hydroxy acids such
as salicylic acid and salicylic acid salts and derivatives), urea, hyaluronic acid, phytic
acid, lipoic acid; lysophosphatidic acid, skin peel agents (e.g., phenol, resorcinol and the
like), vitamin B3 compounds (e.g., niacinamide, nicotinic acid and nicotinic acid salts and
esters, including non-vasodilating esters of nicotinic acid (such as tocopheryl nicotinate),
nicotinyl amino acids, nicotinyl alcohol esters of carboxylic acids, nicotinic acid N-oxide
and niacinamide N-oxide), vitamin B5 and retinoids (e.g., retinol, retinal, retinoic acid,
retinyl acetate, retinyl palmitate, retinyl ascorbate). In the case of dry, scaly skin
(xerosis) and ichthyosis such agents can alleviate the symptoms by temporary relief of
itching associated with these conditions.


Anti-oxidants/radieal scavengers
[00171 ] A safe and effective amount of ah anti-oxidant/radical scavenger can be
added to the compositions according to one or more embodiments of the present
invention, for example, from about 0.1% to about 10%, or from about 1% to about 5% of
the composition.
[00172] Anti-oxidants/radical scavengers such as ascorbic acid (vitamin C) and
ascorbic acid salts, ascorbyl esters of fatty acids, ascorbic acid derivatives (e.g.,
magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbyl sorbate),
tocopherol (vitamin E), tocopherol sorbate, tocopherol acetate, other esters of
tocopherol, butylated hydroxy benzoic acids and their salts, 6-hydroxy-2,5,7,8-
tetramethylchroman-2-carboxylic acid (commercially available under the tradename
Trolox.sup.R), gallic acid and gallic acid alkyl esters, especially propyl gallate, uric acid
and uric acid salts and alkyl esters, sorbic acid and sorbic acid salts, lipoic acid, amines
(e.g., N,N-diethylhydroxylamine, amino-guanidine), sulfhydryl compounds (e.g.,
glutathione), dihydroxy fumaric acid and dihydroxy fumaric acid salts, lycine pidolate,
arginine pilolate, nordihydroguaiaretic acid, bioflavonoids, curcumin, lysine, methionine,
proline, superoxide dismutase, silymarin, tea extracts, grape skin/seed extracts, melanin,
and rosemary extracts may be used.
[00173] The oleaginous foam according to one or more embodiments of the present
invention is suitable for delivering skin protecting and revitalizing anti-oxidants/radical
scavengers. Due to the beneficial properties in the treatment of psoriasis and other skin
inflammation conditions of specific substances, the composition includes a substance
selected from the group consisting of a polyunsaturated fatty acid, containing omega-3
and omega-6 fatty acids (such as linoleic and linolenic acid, gamma-linoleic acid (GLA),
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Likewise, due to their
moisture-retaining and skin protective properties, emollients and silicone oils are
included in the composition according to one or more embodiments of the present
invention. Thus, in one embodiment, a skin protective foam is provided, wherein the
hydrophobic solvent includes in full or in part, a solvent selected from the group
consisting of emollients, silicone oil and oils, rich in unsaturated fatty acids,
therebyaffording a synergistic therapeutic effect of the anti-oxidants/radical scavenger
agent and the vehicle components.
Self-tanning active agents


[00174] The oleaginous foams according to one or more embodiments of the present
invention are particularly suitable for the uniform delivery of a tanning active agent onto
large areas of the skin. The composition includes from about 0.1 % to about 20% of
dihydroxyacetone or any other compound, known in the art as an artificial tanning active
agent
The composition includes from about 2% to about 7%, or from about 3% to about 6%, of
dihydroxyacetone or any other compound, known in the art as an artificial tanning active
agent.
Solid matter agents
[00175] According to one or more embodiments of the present invention, the active
agent is a solid matter or particulate matter. Namely the composition includes a at least
one active agent which is substantially insoluble in the liquid carrier composition of the
foamable composition. For definition purposes, solid matter shall include, but will not be
limited to, material substantially insoluble in the foamable composition.
[00176] A concentration of at least 10% solid matter is included in the
foamable composition. The concentration of the solid matter in the
foamable composition is from about 1% to about 20% w/w or from about
2% to about 16% w/w.
[00177] By way of example, titanium dioxide, zinc oxide, zirconium oxide, iron oxide
and mixtures thereof may be used as solid matter substances Titanium dioxide has an
average primary particle size of from about 15 nm to about 100 nm. Zinc oxide has an
average primary particle size of from about 15 nm to about 150 nm. Zirconium oxide has
an average primary particle size of from about 15 nm to about 150 nm. Iron oxide has
an average primary particle size of from about 15 nm to about 500 nm. In one
embodiment the metal oxides are present in the amount of from about 0.1 % to about
20%, or from about 0.5% to about 16%, or even from about 1% to about 10%, of the
composition. In yet another embodiment, such solids are micronized to form particles
having primary size of less than 15 nm.
[00178] Other suitable solid materials include silicon-containing solid matter such as
silicone oxide, also termed "silica", "fumed silica" and "silica gel", a white or colorless
insoluble solid (Si02); and talc, which is fine grained mineral consisting of hydrated
magnesium silicate; carbon, for example in the form of amorphous carbon or graphite;
oxidizing agents, such as benzoyl peroxide, calcium and magnesium hypochlorite;
metallic silver, in small particles, including nanocrystalline silver, which is used for


antibacterial and wound healing purposes; other metal particles and mineral particles;
cosmetic scrub materials, including, for example meals of strawberry seeds, raspberry
seeds, apricot seeds, sweet almond, cranberry seeds; and pigments, which are insoluble
in the foamable composition.
[00179] When such solid matter agents are included in the oleaginous foamable
composition according to one or more embodiments of the present invention, a foam
product combining the refatting, regulating residence of an active ingredient in the skin
and protective properties of the oleaginous foam carrier and the beneficial properties of
the solid matter agent is afforded.
[00180] Generally, products for the prevention and treatment of diaper dermatitis and
for skin protection are provided in the form of paste intended for application on the
baby's posterior, under the diaper. The paste typically includes about 30% oil and/or
petrolatum, and about 10% zinc oxide, which are intended to provide a protective barrier
between the baby's skin and the irritating environment inside the diaper. While
containing the right ingredients, current baby pastes are very viscous and thick, and
therefore hard to spread on the target area.
[00181] The oleaginous foam for treating or preventing diaper rash according to one
or more embodiments of the present invention includes the following ingredients:
at least one solvent selected from the group consisting of a hydrophobic
solvent, a co-solvent, an emollient and mixtures thereof, at a concentration of about 30%
to about 90%, preferably between about 30% to about 70%
water at a concentration of 1% to about 60%;
about 6% to about 20% zinc oxide (or an alternative metal oxide)
at least one non-ionic lipophilic surface active agent, preferably having an HLB
value of about 3 to about 10, more preferably about 3.5 to about 9 at a concentration of
about 0.1% to about 10%, or between about 0.1% and about 5%;
at least one gelling agent at a concentration of about 0.1% to about 5%;
a liquefied or compressed gas propellant at a concentration of about 3% to
about 25% of the total composition, in an aerosol container.
[00182] Such foam is superior to current pastes in that it is very fluffy and light. Upon
discharge from the aerosol can, it creates a mass, having density between 0.04 gr/mL
and 0.2 gr/mL, which is very easy to spread evenly and uniformly on the target area.



There is no need to rub thoroughly and therefore, application of the foam does not cause
any discomfort to the baby, unlike conventional baby pastes. Following application and
spreading of the foam, a protective layer is formed, which is water resistant, and does
not wash out under a stream of tap water.
[00183] Foam for diaper dermatitis and/or skin protection can further contain anti-
im'tant and/or infective agents, such as corticosteroids, anti-inflammatory, anti-allergic,
anti-fungal and anti-microbial agents.
Skin-Lightening and Whitening Agents
[00184] The foam according to one or more embodiments of the present invention is
particularly suitable for the uniform delivery of a skin-lightening agent. When used, the
compositions may include from about 0.1% to about 10%, or from about 0.2% to about
5%, of the composition, of a skin-lightening agent. Suitable skin lightening or whitening
agents include those known in the art, including hydroquinone, azelaic acid and other
related dicarboxylic acids, and salts and derivatives thereof, retinoids, kojic acid, arbutin,
nicotinic acid and nicotinic acid precursors, salts and derivatives, ascorbic acid and salts
and derivatives thereof (e.g., magnesium ascorbyl phosphate or sodium ascorbyl
phosphate), and herbal extracts (e.g., mulberry extract, placental extract).
[00185] In one or more embodiments of the present invention, the foam composition
includes a combination of at least one skin-whitening agent and at least one additional
active agent selected from retinoids, keratolytically active agents and anti-inflammatory
agents.
[00186] In one or more embodiments, the composition includes a combination of at
least one skin-whitening agent and at least one keratolytically active agent selected from
a alpha-hydroxy acids, beta hydroxy acids, and retinoids.
[00187] In one or more embodiments of the present invention, the foam composition
includes a combination of a skin-whitening agent and an inorganic sunscreen agent.
When inorganic sunscreen agents, e.g. titanium dioxide and zinc oxide, are rubbed onto
the skin, they leave a white coating, which provides an instant (although transient)
whitening effect, which is highly desirable by the consumer, who wishes to see instant
change in his/her appearance. The whitening agent, in combination with the inorganic
sunscreen agent in the foam carrier can be easily and uniformly distributed on the skin
surface, thereby affording an even instant whitening effect, unlike creams that are
difficult to spread evenly on skin areas.


Sunscreens
[00188] Exposure to ultraviolet light can result in excessive scaling and texture
changes of the stratum comeum. The foam composition may be formulated to provide a
composition for the delivery of sunscreen agents by inclusion of a sunscreen active.
Application of a sunscreen foam is very convenient and it spreads easily over large skin
areas. The presence of a hydrophobic solvent in the foam ensures long lasting effect,
even while bathing.
[00189] As used herein, "sunscreen active" includes both sunscreen agents and
physical sunblocks. Suitable sunscreen actives can be organic or inorganic. Inorganic
sunscreens useful herein include metallic oxides such as titanium dioxide having an
average primary particle size of from about 15 nm to about 100 nm, zinc oxide having an
average primary particle size of from about 15 nm to about 150 nm, zirconium oxide
having an average primary particle size of from about 15 nm to about 150 nm, iron oxide
having an average primary particle size of from about 15 nm to about 500 nm, and
mixtures thereof. When used herein, the inorganic sunscreens are present in the
amount of from about 0.1% to about 20% by weight, or from about 0.5% to about 10% by
weight, or from about 1% to about 5% by weight.
[00190] A wide variety of conventional organic sunscreen actives are suitable for use
herein. Specific suitable sunscreen actives include, for example, p-aminobenzoic acid,
p-aminobenzoic acid salts and p-amiriobenzoic acid derivatives (ethyl, isobutyl, glyceryl
esters; p-dimethylaminobenzoic acid); anthranilates (i.e., o-amino-benzoates; methyl,
menthyl, phenyl, benzyl, phenylethyl, linalyl, terpinyl, and cyclohexenyl esters);
salicylates (amyl, phenyl, octyl, benzyl, menthyl, glyceryl, and di-pro-pyleneglycol
esters); cinnamic acid derivatives (menthyl and benzyl esters, a-phenyl cinnamonitrile;
butyl cinnamoyl pyruvate); dihydroxycinnamic acid derivatives (umbelliferone,
methylumbelliferone, methylaceto-umbelliferone); trihydroxy-cinnamic acid derivatives
(esculetin, methylesculetin, daphnetin, and the glucosides, esculin and daphnin);
hydrocarbons (diphenylbutadiene, stilbene); dibenzalacetone and benzalacetophenone;
naphtholsulfonates (sodium salts of 2-naphthol-3,6-disulfonic and of 2-naphthoI-6,8-
disulfonic acids); di-hydroxynaphthoic acid and di-hydroxynaphthoic acid salts; o- and p-
hydroxybiphenyldisulfonates; coumarin derivatives (7-hydroxy, 7-methyl, 3-phenyl);
diazoles (2-acetyl-3-bromoindazole, phenyl benzoxazole, methyl naphthoxazole, various
aryl benzothiazoles); quinine salts (bisulfate, sulfate, chloride, oleate, and tannate);
quinoline derivatives (8-hydroxyquinoline salts, 2-phenylquinoline); hydroxy- or methoxy-


substituted benzophenones; uric and violuric acids; tannic acid and tannic acid
derivatives (e.g., hexaethylether); (butyl carbotol) (6-propyl piperonyl) ether;
hydroquinone; benzophenones (oxybenzene, sulisobenzone, dioxybenzone,
benzoresorcinoi, 2,2,,4,4'-tetrahydroxybenzophendne, 2,2'-dihydroxy-4,4'-
dimethoxybenzophenone,octabenzone;4-isopropyldibenzdylmethane;
butyimethoxydibenzoylmethane; etocrylene; octocrylene; [3-(4'-methylbenzylidene
boman-2-one), terephthalylidene dicamphor sulfonic acid and 4-isopropyl-di-
benzoylmethane.
[00191] An effective amount of the organic sunscreen active is used, typically from
about 1% to about 20% by weight, more typically from about 2% to about 10% by weight
of the composition. Exact amounts will vary depending upon the sunscreen or
sunscreens chosen and the desired Sun Protection Factor (SPF). A composition
containing at least one sunscreen agent having SPF of at least about 15 is useful in
protecting the skin from sunburn. In one or more embodiments, a composition
containing at least one sunscreen agent having SPF of at least about 15, is useful in
preventing a disease comprising skin hyperpigmentation, skin cancer and other skin
bioabnormalities, which are associated with excessive exposure to sun. A composition
containing at least one sunscreen agent having SPF of at least about 30 can be used.
[00192] In one or more embodiments of the present invention, the foam composition
includes a combination of a skin-whitening agent and an inorganic sunscreen agent.
When inorganic sunscreen agents, e.g. zinc oxide and titanium dioxide, are rubbed onto
the skin, they leave a white coating, which provides an immediate (although transient)
whitening effect, which is highly desirable by the consumer, who wishes to see instant
change in his/her appearance. The whitening agent, in combination with the inorganic
sunscreen agent in the foam carrier can be easily and uniformly distributed on the skin
surface, thereby affording an even instant whitening effect, unlike creams, which are
inherently difficult to spread evenly on skin areas.
Use of a solvent, surface active agent, foam adjuvant and polymeric agent as an active
agent.
[00193] According to one embodiment, the active agent is selected from the group
consisting of a solvent, a surface active agent, a foam adjuvant and a gelling agent,
which are, on a case by case basis, known to possess a therapeutic benefit.


Composition and Foam Physical Characteristics
Composition flow properties
[00194] The composition according to one or more embodiments of the present
invention includes water, hydrophobic solvents, formulation excipients and propellant
and form a stable emulsion, which has an shelf-life of at least two years at ambient
temperature. Following accelerated stability studies, they demonstrate desirable texture;
they form fine bubble structures that do not break immediately upon contact with a
surface, spread easily on the treated area and absorb quickly.
[00195] The composition according to one or more embodiments of the present
invention includes a propellant, e.g., a compressed gas or liquid propellant, which is a
low molecular weight hydrocarbon.
[00196] Yet, another property of a composition is level of flow of the composition,
since a non free flowing composition cannot flow through the dip-tube of the aerosol
container and create an acceptable foam. It is known in the art that compositions
comprising semi-solid hydrophobic solvents, e.g., white petrolatum, are excessively
viscous and demonstrate poor flowability.
[00197] According to one or more embodiments of the invention the foamable
composition provides a low specific gravity foam having superior expandability, flow
properties and sheer breakability (among other attributes). According to one or more
embodiments of the present invention, the total amount of at least one surface active
agent, at least one foam adjuvant (optional) and at least gelling agent, in combination
does not exceed 8 % (w/w) of foamable composition. In other embodiments, the
combined amounts of at least one surface active agent, at least one foaming adjuvant
and at least one gelling agent is less than 5 % (w/w) of foam composition. The low solid
content improves the flow properties of the foam, reduces unpleasant skin residue and
reduces the cost of manufacture. As is demonstrated herein, the foam stability and
expandability are excellent, despite the low levels of these components in the foam.
Expandability
[00198] Expandability is a further feature of a product that is intended to treat large
surface areas and internal cavities of the body. Thus, in one embodiment of the present
invention, the specific gravity of the foam, upon discharge from the aerosol can is
between about 0.02 gr/mL and 0.5 gr/mL, or between about 0.04 gr/mL and about 0.2
gr/mL


Foam Physical Characteristics
[00199] An acceptable foam possesses the following consistency and texture
characteristics.,
[00200] Upon release from the aerosol can, a foam mass is created, which is
sustained on a surface for at least one minute, preferably at least two minutes and more
preferably at least three minutes.
[00201 ] Foam texture should vary from a very fine creamy foam to a fine bubble
structure.
[00202] The foam has a specific gravity in the range of about 0.02
gr/mL to about .0.5 gr/mL or between about 0.04 gr/mL and about 0.2
gr/mL.
[00203] An acceptable foam possesses the following spreadability and absorption
characteristics:
The foam does not readily collapse upon dispensing on the skin;
Spreads easily on a skin surface;
Substantially absorbed following rubbing onto the skin.
In terms of organoleptic properties an acceptable foam is one, that:
Creates a pleasant feeling after application;
Leaves minimal oily residue;
Leaves minimal shiny residual look.
[00204] The following scale for foam quality is used to evaluate foams:
E (excellent): very rich and creamy in appearance, does not show any bubble
structure or shows a very fine (small) bubble structure.
G (good): rich and creamy in appearance, very small bubble size, "dulls" more
rapidly than an excellent foam.
FG (fairly good): a moderate amount of creaminess noticeable, bubble structure
is noticeable.
F (fair): very little creaminess noticeable, larger bubble structure than a "fairly
good" foam.



P (poor): no creaminess noticeable, large bubble structure.
VP (very poor): dry foam, large very dull bubbles, difficult to spread on the skin.
[00205] Foams, adequate for topical administration according to one or more
embodiments of the present invention are of quality grade E or G upon release from the
aerosol container. Smaller bubbles are indicative of more stable foam, which does not
collapse spontaneously immediately upon discharge from the container either onto a
surface at ambient temperature or onto a skin surface. The finer foam structure looks
and feels smoother, thus increasing its usability and appeal.
Foam stability and breakability
[00206] In one or more embodiments, the foam compositions are desirably stable for
a long period of time. Thus, the foam composition does not undergo phase separation
following at least two freeze/thaw cycles.
[00207] According to further embodiments, upon discharge from an aerosol can onto
a mucosal membrane at about 37°C, the foam expands to reach the designated volume
of the foam and stays stable as a foam for at least 60 seconds following application, or
about 2 minutes, or even about 3 minutes.
[00208] A further aspect of foam properties, according to one or more
embodiments of the present invention is breakability. Sheer-force
breakability of the foam, as attained by the composition of the present
invention is clearly advantageous to thermally-induced breakability,
present, for example in US Pat. 6,126,920 and W091/11991, and the
respective Olux® and Luxiq® products, as demonstrated by the fact that
according to the use instructions of Olux® and Luxiq®, the foam cannot
be applied on the hand and afterwards delivered to the afflicted area,
since it collapses upon exposure to skin temperature.
Further technical parameters
[00209] The composition according to one or more embodiments of the present
invention can be contained in and dispensed from a container capable of withstanding
the pressure of the propellant gas and having an appropriate valve/nozzle for dispensing
the composition as foam under pressure. A customary liquefied or compressed gas
propellant can be added, in the amount of about 3 to about 25% of the total composition.
Liquefied propellants are gases that exist as liquids under pressure, including high purity


hydrocarbons such as propane, isobutane and n-butane, dimethyl ether and
chlorofluoroearbons (CFCs).
[00210] According to one embodiment, he composition of the present invention is
placed on a patch, tape or the skin-contact compartment of a transdermal delivery
apparatus and applying such object onto the skin, in order to attain effective superficial
treatment or enhanced penetration of the drug into the skin or through the skin.
[00211] Utilizing such strategy, one can apply drugs, which are
currently administered systemically or that require transdermal delivery.
Examples for such drugs are nicotine, testosterone and other male
hormones and male hormone precursors, estrogen and other female
hormones and hormone precursors, growth hormone, insulin, caffeine,
steroidal and non-steroidal anti-inflammatory agents and thyroid
hormone substitutes.
[00212] The therapeutic composition according to the present invention can also be
used to prepare cosmetics for beauty purpose by adding into skin care agents and
perfume.
Metered dosing
[00213] In order to provide proper therapy, precise dosing is advantageous.
According to one embodiment, the foam therapeutic product is adapted for storage in an
aerosol container having a metered dose valve associated therewith for dispensing an
accurate dose of drug in the form of a foam. The metered dose valve is selected to
release a foam in a volume that will allow effective spreading of the active agent
throughout the body surface with substantially minimal overdose.
[00214] In one or more embodiments, the meter dose valve provides a unit dose of
between about 10 µL and about 1000 µL. Assuming a representative foam density
(specific gravity) of 0.06 g/mL, a 10 µL valve provides a volume of about 0.17 mL of
foam, and a 1000 µL metered dose valve provides about 17 mL of foam. Thus, by
selecting a specific metered dosing valve and adjusting the foam density by fine tuning
formulation parameters and adjusting the ration between the liquid components of the
composition and the propellant, one can design an adequate dosage form according to
the specific target body surface.
Fields of Pharmaceutical applications



[00215] By including an appropriate therapeutic agent in the foamable carrier, the
foam composition according to one or more embodiments of the present invention is
useful in treating a patient having a any one of a variety of dermatological disorders (also
termed "dermatoses"), such as classified, in a non-limiting exemplary manner, according
to the following groups:
[00216] Dermatitis including Contact Dermatitis, Atopic Dermatitis, Seborrheic
Dermatitis, Nummular Dermatitis, Chronic Dermatitis of the hands and feet, Generalized
Exfoliative Dermatitis, Stasis Dermatitis; Lichen Simplex Chronicus; Diaper rash;
Bacterial Infections including Cellulitis, Acute Lymphangitis, Lymphadenitis, Erysipelas,
Cutaneous Abscesses, Necrotizing Subcutaneous Infections, Staphylococcal Scalded
Skin Syndrome, Folliculitis, Furuncles, hydradenitis Suppurativa, Carbuncles,
Paronychial Infections, Erythrasma; Fungal Infections including Dermatophyte Infections,
Yeast Infections; Parasitic Infections including Scabies, Pediculosis, Creeping Eruption;
Viral Infections; Disorders of Hair Follicles and Sebaceous Glands including Acne,
Rosacea, Perioral Dermatitis, Hypertrichosis (Hirsutism), Alopecia, including male
pattern baldness, alopecia areata, alopecia universalis and alopecia totalis; ;
Pseudofolliculitis Barbae, Keratinous Cyst; Scaling Papular Diseases including Psoriasis,
Pityriasis Rosea, Lichen Planus, Pityriasis Rubra Pilaris; Benign Tumors including Moles,
Dysplastic Nevi, Skin Tags, Lipomas, Angiomas, Pyogenic Granuloma, Seborrheic
Keratoses, Dermatofibroma, Keratoacanthoma, Keloid; Malignant Tumors including
Basal Cell Carcinoma, Squamous Cell Carcinoma, Malignant Melanoma, Paget's
Disease of the Nipples, Kaposi's Sarcoma; Reactions to Sunlight including Sunburn,
Chronic Effects of Sunlight, Photosensitivity; Bullous Diseases including Pemphigus,
Bullous Pemphigoid, Dermatitis Herpetiformis, Linear Immunoglobulin A Disease;
Pigmentation Disorders including Hypopigmentation such as Vitiligo, Albinism and
Postinflammatory hypopigmentation and Hyperpigmentation such as Melasma
(chloasma), Drug-induced hyperpigmentation, Postinflammatory hyperpigmentation;
Disorders of Comification including Ichthyosis, Keratosis Pilaris, Calluses and Corns,
Actinic keratosis; Pressure Sores; Disorders of Sweating; Inflammatory reactions
including Drug Eruptions, Toxic Epidermal Necrolysis; Erythema Multiforme, Erythema
Nodosum, Granuloma Annulare.
[00217] The oleaginous compositions according to one or more embodiments of the
present invention are useful in the therapy of non-dermatological disorders, where in
transdermal delivery of an active agent is effective against the, non-dermatological


disorders. By way of example, such disorders include localized pain in general, as well
as joint pain, muscle pain, back pain, rheumatic pain, arthritis, osteoarthritis and acute
soft tissue injuries and sports injuries. Other disorders of this class include conditions
treatable by hormone therapy, such as hormone replacement therapy, transdermal
nicotine administration. The foam composition of the present invention is also useful in
the delivery of local anesthetic agents.
[00218] The oleaginous compositions according to one or more embodiments of the
present invention are further useful for the treatment and prevention of disorders and
diseases of other body cavities including the rectum, vagina, penile urethra and ear
canal.
[00219] Thus, the oleaginous foam compositions according to one or more
embodiments of the present invention are useful in treating a patient having any one of a
variety of gynecological disorders, such as classified, in a non-limiting exemplary
manner, according to the following groups:
Pelvic pain, including premenstrual syndrome (PMS),
mittelschmerz (severe midcycle pain due to ovulation), dysmenorrhea
(pain related to the menstrual cycle), endometriosis, ectopic pregnancy,
ovarian cysts and masses, acute pelvic inflammatory disease, pelvic
congestion syndrome and vulvodynia; vulvovaginal infections, including
bacterial vaginosis, candidal vaginitis, trichomonas vaginalis, herpes
simplex genital ulcers and warts, pelvic inflammatory disease (PID),
cervicitis, acute and chronic salpingitis; endometriosis; gynecological
neoplasms, including endometrial Cancer, ovarian cancer, cervical
cancer, vulvar cancer, vaginal cancer, fallopian tube cancer and
gestational trophoblastic disease; benign tumors; sexually transmitted
diseases; sexual dysfunction disorders that respond to pharmacological
therapy, including sexual arousal disorder, female orgasmic disorder,
dyspareunia and vaginismus; and various gynecological disorders that
respond to hormonal therapy.
[00220] The foam according to one or more embodiments of the present invention can
be used as a lubricating foam. Without limitation, the lubricating foam is useful in
lubrication of the birth canal for easy passage of a newborn baby or the vaginal cavity
during intercourse.


[00221] Rectal applications include, for example; anal abscess/fistula, anal cancer,
anal warts, Crohn's disease, haemorrhoids, anal and perianal pruritus, soreness, and
excoriation, perianal thrush, anal fissures, fecal incontinence, constipation, polyps of the
colon and rectum.
[00222] The oleaginous foam compositions according to one or more embodiments of
the present invention are further useful for intra-vaginal and rectal treatment of sexually-
transmitted and non-sexually-transmitted infectious disease (STDs).
[00223] In one or more embodiments, the invention provides a method of treatment of
a disorder of the skin, mucosal membrane, ear channel, vaginal, rectal and penile
urethra disorders, comprising topical application of the foam composition of the present
invention, whereby one or more active agents, in a therapeutically effective concentration
to the afflicted area.
[00224] In a further embodiment, the invention provides a method of
treatment of a non-dermatological disorder, which responds to topical
delivery of an active agent, comprising topical application of the foam
composition of the present invention, whereby one or more active
agents, in a therapeutically effective concentration to the skin.
Treatment / Therapy
[00225] The terms "therapy* and "treatment" as used herein interchangeably, cover
any treatment of a disease or disorder, and includes, for example:
(i) curing the disease or disorder;
(ii) preventing the disease or disorder from occurring in a subject which may
be predisposed to the disease but has not yet been diagnosed as having it;
(iii) inhibiting the disease or disorder;
(iv) relieving the disease or disorder;
(iv) causing regression of the disease;
(v) providing a beneficial immunological effect;
(vi) improving the quality of life of a subject afflicted by a disease or disorder;
and, in the case of cosmetic treatment;


(vii) cleansing, beautifying, promoting attractiveness, or altering the
appearance without affecting the body's structure or functions.
[00226] In the following, some non-limiting examples and experiments are described
in detail. This invention is not limited to these examples and experiments. Many
variations will suggest themselves are within the full intended scope of the appended
claims.
Example 1- Anhydrous foam comprising a potent solvent.
[00227] The components of the anhydrous foam are listed in the table below.


Notes:
- The liquefied or gas propellant can be added at a concentration of about 3% to about
25%.
- The compositions used only non-ionic surface active agents, in a concentration of about
2%, and the total amount of surface active agent, foam adjuvants and polymeric agent
ranged from about 4% to about 6% (w/w).
- The foam of this example having a density of about 0.2 gr/mL is useful as a carrier of
additional active agents. It is also useful as lubricating foam, for various purposes.


- The liquefied or gas propellant can be added at a concentration of about 3% to
about 25%.

- The potent solvent and hexylene glycol (emollient) may be optionally
inGorporated.
- In these particular examples, a minimal water content was used for the gelling
agent incorporation; higher levels of water are an option.
- Lecithin is provided as the surface active agent. Several types of powdered, de-
oiled and liquid (55% to 80% Phosphatidyl choline) phospholids have been tested
successfully for the production of acceptable foams.
- In the current examples, polyvinylpyrrolidone (PVP) was used as the gelling
agent; however, other gelling agents can be used as well.
- The compositions use only non-ionic surface active agents, in concentration of
about 2%, and the total amount of surface active agent, foam adjuvants and
polymeric agent ranged from about 4% to about 6% (w/w).
- The foam of this example is useful as a carrier of additional active agents. It is
also useful as lubricating foam, for various purposes.
- Stearyl alcohol, cetyl alcohol or oleyl alcohol (foam adjuvants) and co-solvents,
such as propylene glycol and hexylene glycol, are optionally incorporated in the
foam.
- Density of the foam is about 0.08 to about 0.40 gr/mL.





In non-limiting examples, the oil/glycerin foams of the present invention contain
about 10% to about 20% water, about 37% glycerin and about 30% oil blend and
about 10% hexylene glycol.
- The compositions use only non-ionic surface active agents, in concentration, of
about 2%, and the total amount of surface active agent, foam adjuvants and
polymeric agent ranged from about 8% to about 12% (w/w).
- The foam of this example is useful as a carrier of additional active agents. It is
also useful as lubricating foam, for various purposes.
- Density of the foam is about 0.18 gr/mL to about 0.20 gr/mL
- Upon release from the aerosol can, foam is released, and stays stable for several
minutes, until it is rubbed onto the afflicted area, then it is immediately broken
down and absorbed. This property enables convenient and even application with
good sensory feeling.
Example 4: Compositions comprising PEG
[00230] Compositions comprising polyethylene glycol (PEG) derivatives have been
prepared and shown to be excellent foams. According to the following non-limiting
example the composition comprises about 80% to about 97.5% PEG 400, about 1% to
about 5% of at least one surface active agent having HLB between 2 and 9 and 0.5%
gelling agent, prior to the addition of a propellant (about 10% of the total composition).
Notably the following compositions did not comprise any water at all.


Notes:
- The liquefied or gas propellant can be added at a concentration of about
3% to about 25%.
- The foams of this example have a non-ionic surface active agent at a
concentration of 2%. Total amounts of surface active agent foam adjuvant and
polymeric agent is in the range of 2.5%.
- The compositions are useful as carriers of various active therapeutic
active agents.
[00231] The following table exemplifies the use of PEG 400 as a potent solvent for
Mupirocin, which is practically insoluble in mineral oil and other commonly used ointment
solvents. Note that Mupirocin is incompatible with most solvents and thus, a foam
comprising PEG 400 as the sole solvent is highly valuable.


The liquefied or gas propellant can be added at a concentration of about 3%' to about
25%.
**The foams of this example have a non-ionic surface active agent at a concentration of "~
2%. Total amounts of surface active agent foam adjuvant and polymeric agent is in the
range of 2.5 % (w/w).

Example 6. Comparison between PEG 400 foamable compositions with and without
gelling agent.
[00232] The compositions of the test articles are provided in the following table. All
foams were dispensed on a warm surface (38°C), and the time to full collapse of the
foam was measured. As shown in the table, it has been strikingly demonstrated that

foam compositions without gelling agent, 100% breakdown occurred within 30, seconds,
while foams containing gelling agent remained, with and without surfactant, were stable
for several minutes.


WE CLAIM:
1. An oleaginous foamable therapeutic composition, comprising :
a. a solvent selected from the group consisting of a hydrophobic solvent, a silicone oil, or
a mixture thereof, wherein said solvent is present at a concentration of 70% to
96.5% by weight of the total composition;
b. a surface-active agent at a concentration of 0.1 % to 10% by weight of the
total composition;
c. a gelling agent at a concentration of 0.1 % to 5% by weight of the total
composition;
d. a therapeutically effective amount of an active agent;
e. a propellant at a concentration of 3% to 25% by weight of the total •
composition.
2. The oleaginous foamable therapeutic composition as claimed in claim 1, comprising a
foam adjuvant selected from the group consisting of a fatty alcohol having at least 15
carbon atoms and a fatty acid having at least 16 carbon atoms.
3. The oleaginous foamable therapeutic composition as claimed in claim 1, wherein said
solvent comprises a hydrophobic solvent having a degree of solubility of less than
one gram of solvent per 100 ml of distilled water at ambient temperature.
4. The oleaginous foamable therapeutic composition as claimed in claim 1, wherein said
solvent comprises a hydrophobic solvent selected from the group consisting of a
mineral oil, a triglyceride oil, a silicone oil, a polyunsaturated oil, an unsaturated oil and
an essential oil.
5. The oleaginous foamable therapeutic composition as claimed in claim 1, wherein said
solvent comprises at least one hydrophobic solvent and wherein the composition
comprises at least one co-solvent.

6. The oleaginous foamable therapeutic composition as claimed in claim 5, wherein said
the hydrophobic solvent and the co-solvent are present in the composition in a weight
ratio of 1:8 to 8:1 of said hydrophobic solvent to said co-solvent.
7. The oleaginous foamable therapeutic composition as claimed in claim 5, wherein said
co-solvent is selected from the group consisting of polyols, sulfoxides, oleates, lactam
compounds, esters, amides, alkanoic acids, and alkanols and admixtures thereof..
8. The oleaginous foamable therapeutic composition as claimed in claim 5, wherein the
hydrophobic solvent and the co-solvent form an emulsion.
9. The oleaginous foamable therapeutic composition as claimed in claim 5, wherein said
co-solvent comprises glycerin.
10. The oleaginous foamable therapeutic composition as claimed in claim 9, wherein said
mixture of at least one hydrophobic solvent and glycerin comprises a weight ratio of
1:4 to 4:1.
11. The oleaginous foamable therapeutic composition as claimed in claim 9, wherein said
mixture of at least one hydrophobic solvent and glycerin comprises a weight ratio of
1:2 to 2:1.
12. The oleaginous foamable therapeutic composition as claimed in claim 5, wherein said
co-solvent comprises a polyethylene glycol.
13. The oleaginous foamable therapeutic composition as claimed in claim 1, wherein the
composition comprises a potent solvent..
14. The oleaginous foamable therapeutic composition as claimed in claim 13, wherein said
potent solvent solubilizes the active agent at a degree at least 5 times greater than the
degree that mineral oil solubilizes the active agent.
15. the oleaginous foamable therapeutic composition as claimed in claim 13, wherein said -
potent solvent solubilizes the active agent at a degree at least 10 times greater than the
degree that mineral oil solubilizes the active agent

16. The oleaginous foamable therapeutic composition as claimed in claim 13, wherein said
potent solvent is selected from the group consisting of a polyol, polyethylene glycol,
propylene glycol, hexylene glycol, butanediols and isomers thereof, glycerol, benzyl
alcohol, DMSO, ethyl oleate, ethyl caprylate, diisopropyl adipate, dimethylacetamide, N-
methylpyrrolidone, N-hydroxyethylpyrroIidone, polyvinylpyrrolidone, isosorbide
derivatives, dimethyl isosorbide, glycofurol and ethoxydiglycol (transcutol) and mixture
thereof in any propostion.
17. The oleaginous foamable therapeutic composition as claimed in claim 14 or 15, wherein
said potent solvent is a polyol and said active active agent is mupirocin.
18. The oleaginous foamable therapeutic composition as claimed in claim 13, wherein said
potent solvent is a liquid polyethylene glycol.
19. The oleaginous foamable therapeutic composition as claimed in claim 1, wherein, said
surface active agent comprises at least one non-ionic surface active agent
20. The oleaginous foamable therapeutic composition as claimed in claim 19, comprising an
ionic surface-active agent
21. The oleaginous foamable therapeutic composition as claimed in claim 20, wherein said
non-ionic surface-active agent and said ionic surface-active agent are present at'a
weight ratio of 20:1 to 1:1 non-ionic surface active agent to ionic surface
active agent
22. The oleaginous foamable therapeutic composition as claimed in claim 1, wherein the
concentration of said surface-active agent is less than 2% of the entire
composition.
23. The oleaginous foamable therapeutic composition as ciaimed in claim 1, wherein the
surface-active agent comprises a phospholipid.
24. The oleaginous foamable therapeutic composition as claimed in claim 23, wherein the
phospholipid comprises phosphatidylcholine.

25. The oleaginous foamable therapeutic composition as claimed in claim 1, wherein said
gelling agent is selected from the group consisting of a natural polymeric material, a
semi-synthetic polymeric material, a synthetic polymeric material, an inorganic gelling
agent and any mixture thereof.
26. The oleaginous foamable therapeutic composition as claimed in claim 1, wherein the
oleaginous foamable therapeutic composition comprises less than 20% by weight
of water.
27. The oleaginous foamable therapeutic composition as claimed in claim 26, having a
specific gravity of 0.01 gr/ml to 0.4 gr/mL upon release from said
pressurized container.
28. The oleaginous foamable therapeutic composition as claimed in claim 1, wherein said
active agent is selected to treat a dermatological or mucosal disorder.
29. The oleaginous foamable therapeutic composition as claimed in claim 28, wherein said
disorder is selected from the group consisting of a bacterial disorder, a fungal disorder,
a viral disorder, a parasitic disorder, an inflammatory disorder, an autoimmune disorder,
an allergic disorder, a hormonal disorder, a malignant disorder, a cosmetic abnormality
and any combination thereof.
30. The oleaginous foamable therapeutic composition as claimed in claim 1, wherein the.
active agent is a component of the foamable composition selected from the group
consisting of a solvent, a surface-active agent, a gelling agent and a foam adjuvant
31. The oleaginous foamable therapeutic composition as claimed in claim 28, wherein said
therapeutic agent is selected from the group consisting of an anti-infective, an
antibiotic, an antibacterial agent, an antifungal agent, an antiviral agent, an antiparasitic
agent, an antiinflammatory agent, an immunosuppressive agent, an immunomodulator,
an immunoregulating agent, a hormonal agent, vitamin A, a vitamin A derivative, vitamin
B, a vitamin B derivative, vitamin C, a vitamin C derivative, vitamin D, a vitamin D

derivative, vitamin E, a vitamin E derivative, vitamin F, a vitamin F derivative, vitamin K,
a vitamin K derivative, a wound heaiing agent, a disinfectant, an anesthetic, an
analgesic, an antiallergic agent, a corticosteroid, a non-steroidal anti-inflammatory drug,
an alpha hydroxyl acid, a beta-hydroxy acid, a protein, a peptide, a neuropeptide, a
allergen, an immunogenic substance, a haptene, an oxidizing agent an antioxidant, a
retinoid, an antiproliferative agent, an anticancer agent, a photodynamic therapy agent,.,
an anti-wrinkle agent, a radical scavenger, a self-tanning agent, a skin whitening agent,
a skin protective agent, an anti-cellulite agent, a massaging oil and an anti-wart agent, a
refatting agent, a lubricating agent and mixtures thereof.
32. The oleaginous foamable therapeutic composition as claimed in claim 28, wherein the
therapeutic agent is selected for the treatment of a disorder of the skin, mucosal
membrane, ear channel, vagina, penile urethra, colon and rectum.
33. The oleaginous foamable therapeutic composition as claimed in claim 28, wherein the
cosmetic agent is selected from the group consisting of a retinoid, an anti-wrinkle agent,
a radical scavenger, a setf-tanning agent, a skin whitening agent, a skin protective
agent, an anti-cellulite agent, a massaging.oil-and-an anti-wart- agent.
34. The oleaginous composition as claimed in claim 1, wherein the therapeutic agent is
intended for transdermal delivery.
35. The oleaginous foamable therapeutic composition as claimed in claim 1, wherein the
active agent comprises an inorganic solid matter.
36. The oleaginous foamable therapeutic composition as claimed in claim 35, wherein the
inorganic solid matter comprises a metal oxide selected to form a protective layer on a
body surface or a mucosal membrane.
37. The oleaginous foamable composition as claimed in claim 1, comprising water, wherein
the composition is an water-in-oil emulsion; and wherein the surface active agent
comprises a lipophilic surface-active agent having an HLB value of 3 to 10.

38. The oleaginous foamable water-in-oil emulsion as claimed in claim 37, comprising a
foam adjuvant selected from the group consisting of fatty alcohols having greater than
or equal to 15 carbons and fatty acids having greater than or equal to 16 carbons.
39. The oleaginous foamable water-in-oii emulsion as claimed in ciaim 37, wherein the
solvent comprises a hydrophobic solvent having solubility in distilled water at ambient
temperature of less than one gram per 100 ml.
40. The oleaginous foamable water-in-oil emulsion as claimed in claim 37, wherein the
hydrophobic solvent is selected from the group consisting of mineral oil, a triglyceride
oil, an ester of a fatty acid, an ester of a dicarboxylic acid, a silicone oil, a
polyunsaturated oil, an unsaturated oil and an essential oil.
41.The oleaginous foamable water-in-oil emulsion as claimed in claim 37, wherein the
hydrophobic solvent and water are present at a weight ratio in the range of 1-3 to
6:1.
42. The oleaginous foamable water-in-oil emulsion as claimed in claim 37, wherein the
composition comprises a potent solvent selected from the group consisting of
hydrophobic solvents other than mineral oil, wherein the potent solvent solubilizes an
active agent substantially better than mineral oil solubilizes the active agent
43. The oleaginous foamable water-in-oil emulsion as claimed in claim 42, wherein the .
potent solvent solubilizes the active agent at least 5-fold better than mineral oil
solubilizes the active agent.
44. The oleaginous foamable water-in-oil emulsion as claimed in claim 42, wherein said
potent solvent solubilizes the active agent at least 10-fold better than a mineral oil
solubilizes the active agent.
45. The oleaginous foamable water-in-oil emulsion as claimed in claim 42, wherein the
potent solvent is selected from the group consisting of polyols, polyethylene glycols,
propylene glycols, hexylene glycols, butanediols and isomers thereof, glycerols, benzyl

alcohol, DMSO, ethyl oleates, ethyl caprylates, diisopropyl adipate, dimethylacetamides,
N-methylpyrroIidones N-hydroxyethylpyrrolidones, polyvinylpyrrolidones, an isosorbide
derivatives, glycofurols and ethoxydiglycols (transcutol) and mixtures thereof in any
proportion.
46. The oleaginous foamable therapeutic composition as claimed in claim 37 , wherein, said
surface active agent comprises at least one non-ionic surface active agent
47. The oleaginous foamable therapeutic composition as claimed in claim 46, comprising
an ionic surface-active agent.
48.The oleaginous foamable water-in-oil emulsion as claimed in claim 37, wherein the
concentration of the surface-active agent is less than 2 % .
49.The oleaginous foamable water-in-oil emulsion as claimed in claim 37, wherein said
surface-active agent is selected from the group consisting of sorbitan derivatives;
alkoxylated alcohols; hydroxylated derivatives of polymeric silicones; alkylated
derivatives of hydroxylated polymeric silicones; glyceryl esters; beeswax derivatives;
lecithin; and mixtures thereof.
50. The oleaginous foamable water-in-oil emulsion as claimed in claim 37, wherein the
composition comprises a co-solvent selected from the group consisting of polyols,
sulfoxides, oleates, lactam compounds, esters, amides, alkanoic acids, and alkanols
and admixtures thereof.
51. The oleaginous foamable water-in-oil emulsion as claimed in claim 37, wherein the
gelling agent is selected from the group consisting of natural polymeric materials, semi-
synthetic polymeric materials, synthetic polymeric materials, inorganic gelling agents
and mixtures thereof.
52. The oleaginous foamable water-in-oil emulsion as claimed in claim 51, wherein the
inorganic gelling agent comprises silicone dioxide.

53. The oleaginous foamable water-in-oil emulsion as claimed in claim 37, having a specific
gravity of 0.01 gr/ml to 0.4 gr/ml, upon extrusion from a pressured
container.
54.The oleaginous foamable water-in-oil emulsion as claimed in claim 37, wherein the
active agent is a component of the foamable composition and is selected from the
group consisting of a solvent, a surface-active agent, a gelling agent and a foam
adjuvant.
55.The oleaginous foamable water-in-oil emulsion as claimed in claim 37 wherein the
active agent is selected from the group consisting of an an anti-infective, an antibiotic,
an antibacterial agent an antifungal agent, an antiviral agent, an antiparasitic agent, an
antiinflammatory agent an immunosuppressive agent, an immunomodulator, an
immunoregulating agent a hormonal agent, vitamin A, a vitamin A derivative, vitamin B,
a vitamin B derivative, vitamin C, a vitamin C derivative, vitamin D, a vitamin D
derivative, vitamin E, a vitamin E derivative, vitamin F, a vitamin F derivative, vitamin
K, a. vitamin K derivative, a wound healing agent a disinfectant an anesthetic, an
analgesic, an antiallergic agent, a corticosteroid, a non-steroidal anti-inflammatory drug,
an alpha hydroxy! acid, a beta-hydroxy acid, a protein, a peptide, a neuropeptide, a
allergen, an immunogenic substance, a haptene, an oxidizing agent, an antioxidant a
retinoid, an antiproliferative agent an anticancer agent, a photodynamic therapy agent,
an anti-wrinkle agent a radical scavenger, a self-tanning agent, a skin whitening agent,
a skin protective agent, an anti-cellulite agent, a massaging oil and an anti-wart agent, a
refatting agent, a lubricating agent and mixtures thereof.
56.The oleaginous foamable water-in-oil emulsion as claimed in claim 37, wherein the
therapeutic agent is selected for the treatment of a disorder of the skin, mucosal
membrane, ear channel, vagina, penile urethra and rectum.

57. The oleaginous foamable water-in-oil emulsion as claimed in claim 37, wherein the
composition is useful for treating a dermatological. or mucosal disorder and wherein the
etiology of the dermatological or mucosal disorder is bacterial, fungal, viral, parasitic,
inflammatory, autoimmune, allergic, hormonal, malignant and combinations thereof.
58.The oleaginous foamable water-in-oil emulsion as claimed in claim 37, wherein active
agent is an inorganic solid matter.
59. The oleaginous foamable water-in-oil emulsion as claimed in claim 58, wherein the
inorganic solid matter is selected to form a protective layer on a body surface, a body
cavity or a mucosal membrane.
60. The oleaginous foamable water-in-oil emulsion as claimed in ciaim 59, wherein the
inorganic solid matter is selected to treat a skin disorder selected from sensitive skin,.
diaper rash and diaper dermatitis.
61. The oleaginous foam composition as claimed in claim 37, wherein the composition is
useful for treating; or preventing diaper rash and comprises 6 % to 20 %.
metal oxide
62. The oleaginous foamable water-in-oil emulsion as claimed in claim 61, wherein said
metal oxide is zinc oxide.
«
63. The oleaginous foamable water-in-oil emulsion as claimed in claim 61, wherein said
surface active agent has an HLB value of 3.5 to 9.
64. The oleaginous foamable water-in-oil emulsion as claimed in claim 61, wherein the
concentration of said surface active agent at a concentration of 0-1% to 5 % -
65. The oleaginous foamable water-in-oil emulsion as claimed in claims 1 to 64 comprising
less then 5% of a short chain alcohols having up to 5 carbon atoms in the short
chain alcohol carbon chain.

66. An oleaginous foam compositions as claimed in any of claims 1 to 64 for treating,
alleviating or preventing a dermatological, cosmetic or mucosal disorder.
67. A therapeutic device, comprising a pressurized can, equipped with a metered dose
valve and an actuator capable of dispensing a foam, and containing an oleaginous foam
composition as claimed in any of claims 1 to 66.
68. The device as claimed in claim 67, wherein the metered dose valve provides a unit dose
of between 10 µL and 1000 µL.
69. The device as claimed in claim 67, wherein the metered dose valve provides a unit dose
of between 50 µL and 250 µL.
70.A kit comprising a packaging material and contained therein an oleaginous foamble
composition as claimed in any of claims 1 to 65 in a container wherein said gelling
agent is capable of thickening the composition;
wherein said propellant is capable of forming a foam upon release of the composition
from the container and
wherein said packaging material comprising a label which indicates that said composition
can be used for the treatment of a given superficial disorder, which preferably responds to
treatment by said active agent, delivered in an oleaginous vehicle, in a therapeutically effective
dose.


The invention relates to stable oleaginous cosmetic or therapeutic foam compositions containing certain active
agents, having unique therapeutic properties and methods of treatment using such compositions. The foamable composition includes
at least one solvent selected from the group consisting of: a hydrophobic solvent, a silicone oil, an emollient, a co-solvent,
and mixtures thereof, wherein the solvent is present at a concentration of about 70% to about 96.5% by weight of the total composition,
at least a non-ionic surface-active agent at a concentration of about 0.1 % to less than about 10% by weight of the total
composition; at least one gelling agent at a concentration of about 0.1% to about 5% by weight of the total composition; a therapeutically
effective amount of at least one active agent; and at least one liquefied or compressed gas propellant, at a concentration of
about 3% to about 25% by weight of the total composition.

Documents:

02000-kolnp-2006-abstract.pdf

02000-kolnp-2006-claims.pdf

02000-kolnp-2006-correspondence others.pdf

02000-kolnp-2006-correspondence-1.1.pdf

02000-kolnp-2006-correspondence-1.2.pdf

02000-kolnp-2006-description(complete).pdf

02000-kolnp-2006-form-1.pdf

02000-kolnp-2006-form-18.pdf

02000-kolnp-2006-form-3.pdf

02000-kolnp-2006-form-5.pdf

02000-kolnp-2006-general power of authority.pdf

02000-kolnp-2006-international publication.pdf

02000-kolnp-2006-pct form.pdf

02000-kolnp-2006-prioriti document.pdf

2000-KOLNP-2006-ABSTRACT.pdf

2000-kolnp-2006-assignment.pdf

2000-KOLNP-2006-CANCELLED DOCUMENTS.pdf

2000-KOLNP-2006-CLAIMS_1.0.pdf

2000-KOLNP-2006-CLAIMS_1.1.pdf

2000-kolnp-2006-correspondence.pdf

2000-KOLNP-2006-DESCRIPTION COMPLETE.pdf

2000-kolnp-2006-examination report.pdf

2000-KOLNP-2006-FORM 1.pdf

2000-KOLNP-2006-FORM 13-1.1.pdf

2000-kolnp-2006-form 13.2.pdf

2000-KOLNP-2006-FORM 13.pdf

2000-kolnp-2006-form 18.pdf

2000-kolnp-2006-form 3.1.pdf

2000-KOLNP-2006-FORM 3.pdf

2000-kolnp-2006-form 5.pdf

2000-KOLNP-2006-FORM-27.pdf

2000-kolnp-2006-gpa.pdf

2000-kolnp-2006-granted-abstract.pdf

2000-kolnp-2006-granted-claims.pdf

2000-kolnp-2006-granted-description (complete).pdf

2000-kolnp-2006-granted-form 1.pdf

2000-kolnp-2006-granted-specification.pdf

2000-KOLNP-2006-OTHER DOCUMENT-1.1.pdf

2000-KOLNP-2006-OTHERS.pdf

2000-kolnp-2006-others1.1.pdf

2000-KOLNP-2006-PETITION UNDER RULE 137.pdf

2000-KOLNP-2006-REPLY TO EXAMINATION REPORT.pdf

2000-kolnp-2006-reply to examination report1.1.pdf


Patent Number 248223
Indian Patent Application Number 2000/KOLNP/2006
PG Journal Number 26/2011
Publication Date 01-Jul-2011
Grant Date 28-Jun-2011
Date of Filing 17-Jul-2006
Name of Patentee FOAMIX LTD.
Applicant Address P.O. BOX 4038, WEIZMANN-SCIENCE PARK, BUILDING 14, 74140 NESS ZIONA
Inventors:
# Inventor's Name Inventor's Address
1 TAMARKIN DOV HAR HILA STREET 537, 70400 MACCABIM
2 EINI MEIR HASHAKED STREET 2, 74104 NESS ZIONA
3 BOSONOV ALEX GOLDBERG STREET 1, 72683 REHOVOT
4 FRIEDMAN DORON ALON STREET 33, 99797 KARMEI-YOSEF
PCT International Classification Number A61K 9/00
PCT International Application Number PCT/IB2004/004464
PCT International Filing date 2004-12-16
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 60/530,015 2003-12-16 U.S.A.
2 10/835,505 2004-04-28 U.S.A.