Note: Descriptions are shown in the official language in which they were submitted.
1
COMPOSITIONS FOR TREATING INFECTIONS
Field of the invention
[0001] The present invention relates to compositions and in particular to
compositions for
treating a skin or mucosal membrane infection.
Background of the invention
[0002] Any discussion of the prior art throughout the specification should in
no way be
considered as an admission that such prior art is widely known or forms part
of the common
general knowledge in the field.
[0003] Microorganisms and viruses are responsible for a variety of diseases
and disorders in
humans and animals, including many dermatological disorders. Dermatophytes,
for example,
are a group of fungi that cause skin diseases in animals and humans. They
include the genera
Microsporum, Epidermophyton and Trichophyton. Tinea is a term used to describe
a variety of
skin mycoses including tinea pedis (commonly referred to as "athlete's foot"),
tinea corporis
(infections of the trunk, arms and legs), tinea manuum '(infections of the
finger webs), tinea
cruris (infections of the groin), tinea barbae (infections of the neck) and
tinea capitis (infections
of the scalp).
[0004] Viruses are also responsible for a number of skin infections in animals
and humans.
Skin lesions such as warts, cold sores and shingles are often caused by viral
infections. Most
primary viral infections arise from one of three groups of viruses; poxviruses
(poxviridae),
herpesviruses (herpesviridae) and human papillomaviruses (papillomaviridae).
[0005] Common warts are a benign form of tumour typically caused by human
papillomaviruses
(HPV). Some strains of HPV, however, are also etiological agents in dysplasia
and carcinomas
in the oral and genital mucosa.
[0006] Molluscuum contagiosum is a type of poxvirus that causes skin lesions,
sometimes
referred to as water warts. Water warts are characterised by small, discrete,
lobulated
epidermal outgrowths that occur at various locations on the body.
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[0007] Herpes zoster, commonly referred to as shingles, is a skin lesion
caused by infection
from the herpesviridae family of viruses. Shingles is often characterised by a
painful rash and
localised blistering which can last for several months.
[0008] Herpes Simplex Type 1 (HSV1) and Herpes Simplex Type 2 (HSV2) are
etiological
agents of cold sores and genital herpes, respectively. However, both types of
herpes simplex
virus (HSV) can be present on the mouth and genital areas, and it is possible
for an individual to
be infected by both HSV1 and HSV2. Infection by one strain does not render an
individual
immune to the other.
[0009] Recurrent outbreaks of HSV often follow a staged progression involving
prodrome,
vesicle formation, ulceration, crusting and healing. Prodrome is typically
characterised by a
short period of tingling, itching, numbness or burning with no clearly visible
indication of an
infection or outbreak. Vesicle formation involves the development of fluid-
filled blisters, often in
a cluster, and usually surrounded by sore, red skin. Ulceration occurs when
the blisters open to
form painful ulcers or open sores often with a yellow crust at the edges of
the sore. At the
crusting stage, weeping sores or ulcers are covered by a crust or scab.
Healing involves the
disappearance of the crust, swelling, pain and itching. Skin eruptions caused
by viral infection,
particularly HSV, generally have a normal infective course that lasts from
between 10 and 60
days depending on the species of infective virus and the anatomical location
of the infection.
[0010] After an initial outbreak of HSV, the virus may lie dormant in the skin
or in nerve tissue
until triggered to cause a new eruption or site infection. Triggers may
include stress, fever,
sunlight, hormonal changes or certain foods or drugs. When the virus is
reactivated, it typically
causes a sore at the site where it first entered the body.
[0011] Presently, there is no effective vaccine to prevent herpes infection.
Moreover, the ability
of the herpes virus to retreat into the nervous system makes it difficult to
eliminate from the
body. Systemic treatment of viral and fungal infections, although effective in
some cases, may
be associated with health risks including cardiac or hepatic toxicity, nausea,
headaches and
adverse drug interactions. Physical treatments such as cryotherapy, laser
therapy and surgical
removal, while also effective in some cases, can be painful and distressing,
particularly for
children, and may increase the likelihood of scar tissue formation. Topical
antiviral formulations
have also been developed, however, many suffer from problems such as poor
stability leading
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to limited shelf-life, susceptibility to freezing, poor active ingredient
solubility or inefficient
delivery of the active ingredient.
[0012] In this context, there is a need for alternative methods and
compositions for treating skin
and mucosal membrane infections, and in particular, infections caused by
viruses and fungi. It
is an object of the present invention to overcome or ameliorate at least one
of the
disadvantages of the prior art or to provide a useful alternative.
Summary of the invention
[0013] In a first aspect, the present invention provides a composition for
treating a skin or
mucosal membrane infection the composition comprising:
glycerol;
at least one surfactant;
an alcohol;
a terpene or terpenoid compound; and
a copper compound.
[0014] The terpene or terpenoid compound may be present in or extracted from
an
essential oil.
[0015] The essential oil may be obtained from a camphor laurel tree, a kapur
tree, a
rosemary plant, a mint plant, a eucalyptus tree or a tea tree.
[0016] Preferably, the terpene or terpenoid compound is camphor.
[0017] In one or more embodiments, the terpene or terpenoid compound is
menthol.
[0018] In further embodiments, the terpene or terpenoid compound is camphor or
menthol.
[0019] In another embodiment, the composition comprises camphor and menthol.
[0020] The copper compound is preferably selected from the group consisting of
copper
gluconate, copper carbonate, copper sulphate, copper chloride and copper
salicylate.
[0021] The copper compound may be copper sulphate. Preferably, the copper
sulphate is
copper sulphate pentahyd rate.
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[0022] In one or more embodiments, the alcohol is isopropyl alcohol.
[0023] The composition may further comprise Hypericum perforatum extract.
[0024] The composition may further comprise Calendula officinalis extract.
[0025] In one or more embodiments, the composition further comprises aloe
vera.
[0026] Preferably, the composition further comprises vitamin E.
[0027] The at least one surfactant preferably comprises polyethylene glycol.
[0028] The at least one surfactant may comprise polysorbate 80.
[0029] In one or more embodiments, the composition comprises substantially no
water.
[0030] in another aspect, the present invention provides a method of producing
a composition
comprising the steps of:
i) combining glycerol and a copper compound to produce a glycerol solution;
ii) dissolving a terpene or terpenoid compound in an alcohol to produce an
alcohol
solution;
iii) combining the glycerol solution and the alcohol solution; and
iv) adding at least one surfactant.
[0031] Step i) preferably includes heating the glycerol solution to about 80
C.
[0032] Preferably, step i) further comprises adding aloe vera to the glycerol
solution.
[0033] In one or more embodiments, step iv) further comprises adding vitamin
E, Hypericum
perforatum extract and Calendula officinalis extract.
[0034] In another aspect, the present invention provides a method of treating
a skin or mucosa]
membrane infection comprising topically applying the composition of the first
aspect to the skin
or mucosal membrane infection.
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[0035] The skin or mucosal membrane infection may be caused by a bacterium, a
virus or a
fungus.
[0036] Preferably, the skin or mucosal membrane infection is caused by a
virus.
[0037] The virus may be a Herpes Simplex Virus. Preferably, the virus is
Herpes Simplex Virus
1 or Herpes Simplex Virus 2.
[0038] In another aspect, the present invention provides use of a composition
of the first aspect
in the manufacture of a medicament for the treatment of a skin or mucosal
membrane infection.
[0039] In a further aspect, the present invention provides a composition of
the first aspect for
use in the treatment of a skin or mucosal membrane infection.
Detailed description of an embodiment of the invention
[0040] Copper is known to possess antimicrobial and antiviral properties (eg,
Sagripanti et al.
(1997) Mechanism of Copper-Mediated Inactivation of Herpes Simplex Virus.
Antimicrobial
Agents and Chemotherapy 41(4): 812-817; Borkow and Gabbay (2009) Copper, an
ancient
remedy returning to fight microbial, fungal and viral infections. Curr. Chem.
Biol. 3: 272-278).
However, high concentrations of copper may cause blood poisoning which can
potentially be
fatal. Moreover, copper is prone to precipitation and, as such, is often
formulated with relatively
large volumes of water. In contrast, the present inventors have surprisingly
found that
compositions comprising copper and a terpene or terpenoid compound, in
addition to glycerol, a
surfactant and an alcohol, can be formulated with little or no water and that
such compositions
are effective in the treatment of skin and mucosal membrane infections.
Accordingly,
compositions of the present invention comprise:
glycerol;
at least one surfactant;
an alcohol;
a terpene or terpenoid compound; and
a copper compound.
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[0041] A number of different copper compounds may be used in accordance with
the present
invention. The copper compound may be a copper (1) compound or a copper (II)
compound. In
one or more embodiments, the copper compound is copper gluconate, copper
carbonate,
copper sulphate, copper chloride or copper salicylate. Preferably, the copper
compound is
copper sulphate and, more preferably, copper sulphate pentahydrate.
[0042] The composition may comprise from about 1% to about 10% by weight of
the copper'
compound. Preferably, the composition comprises less than about 5% of the
copper
compound, such as from about 2% to about 4% by weight of the copper compound
and,
preferably, about 3% by weight of the copper compound.
[0043] The composition preferably includes a skin protectant such as glycerol.
Glycerol may
form a barrier over the skin and protect against irritation caused by
touching, scratching, rubbing
and the like. It may also provide a protective barrier over the lesion,
preventing loss of the
active ingredient. In one or more embodiments, the composition comprises at
least 20% by
weight of glycerol, such as at least 30% by weight, at least 35% by weight, at
least 40% by
weight, at least 45% by weight or, more preferably, at least 50% by weight of
glycerol.
[0044] The composition preferably includes a terpene or terpenoid compound.
Terpenes and
terpenoids are diverse classes of organic compounds that are widespread in
nature, particularly
in plants, plant parts or plant oils, from which they may be extracted.
Terpenes and terpenoids
can also be synthesised. Terpenes and terpenoids have been shown to possess
antimicrobial
properties (eg, Chaumont and Leger (1992) Campaign Against Allergic Moulds in
Dwellings,
Inhibitor Properties of Essential Oil Geranium "Bourbon" Citronellol, Geraniol
and Citral. Ann.
Pharm. Fr. 50(3): 156-166; Mikhlin et al. (1983) Antifungal and Antimicrobial
Activity of Some
Derivatives of Beta-lonone and Vitamin A. Prikl Biokhim Mikrobiol 19: 795-803;
Kim etal. (1995)
Antibacterial Activity of Some Essential Oil Components Against Five Foodborne
Pathogens. J.
Agri. Food Chem. 43: 2839-2845; lsman (2000) Plant essential oils for pest and
disease
management. Crop Protection. 19: 603-608). They have also been associated with
the effective
treatment of tumors (eg, Crowell et al. (1996) Antitumorigenic Effects of
Limonene and Perillyl
Alcohol Against Pancreatic and Breast Cancer. Adv. Exp. Med. Biol. 401: 131-
136) and the
lowering of cholesterol levels (eg, Elson et al. (1994) The Chemoprevention of
Cancer by
Melavonate-Derived Constituents of Fruits and Vegetables. J. Nutr. 124: 607-
614).
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[0045] The building block of terpenes and terpenoids is the C-5 hydrocarbon,
isoprene (C5H8).
The isoprene building blocks may be joined in a head-to-tail arrangement,
thereby forming linear
or branched chains, or they may be arranged as a ring. Whereas terpenes are
generally
hydrocarbons, terpenoids often contain additional functional groups.
Terpenoids may result
from the modification of a terpene such as when a methyl group has been moved
or removed,
or when an oxygen or other functional group has been added. However, the term
"terpene" is
often used interchangeably with the term "terpenoid".
[0046] The terpene or terpenoid compound may be present in, or extracted from,
an essential
oil. Essential oils are typically extracted from plants, or plant parts, and
may comprise a volatile
mixture of esters, alcohols, vitamins, aldehydes, ketones, terpenes and
terpenoids. They are
usually hydrophobic and immiscible in water. They may, however, be soluble in
certain oils and
organic solvents such as alcohols or acetone. Essential oils for use in the
present invention
may be extracted from, for example, a camphor laurel tree, a kapur tree, a
rosemary plant, a
mint plant, a eucalyptus tree or a tea tree. Other sources of essential oils
may include Plantago
(eg, Plantago major), Hypericum (eg, Hypericaceae perforatus), Baptisia,
Calendula (eg,
Calendular officinalis), myrrh, echinacea (eg, Echinaceae angustifoliae radix
or Echinaceae
purpurea), Phytolaca, Salvia, Tsuga, Styrax, Catechu black, Krameria,
Crataegus, Glycerrhiza
(eg, Glycerrhiza glabra), Angelica, Krameria, Matricaria, Mallow, sage,
chamomile,
Hammamelis, aloe vera, nettle. Kava Kava, Noni fruit (Morinda citrifolia),
Feverfew (eg,
Tanacetum parthenolide), Astragulus, cinnamon, cajeput, fennel, geranium,
girofle, lavender,
lemon, myrte, oregano, pine, sarriette, thyme, Pinus, Star anise and garlic.
[0047] Terpenes that may be suitable for use in accordance with the present
invention include,
for example, hemiterpenes, monoterpenes, sesquiterpenes, diterpenes,
sesterterpenes,
triterpenes, sesquarterpenes, tetraterpenes and polyterpenes. Terpenoids that
may be suitable
for use in accordance with the present invention include, for example,
hemiterpenoids,
monoterpenoids, sesquiterpenoids, diterpenoids, sesterterpenoids,
triterpenoids, tetraterpenoids
and polyterpenoids. In one or more embodiments, the terpene or terpenoid
compound of
the present invention is camphor (C10H180). Camphor may be synthesised or it
may be
extracted from a plant oil such as the oil of the camphor laurel tree
(Cinnamomum
camphora), the kapur tree or rosemary (Rosmarinus officinalis). The camphor is
preferably
provided in a powder or granulated form such as tablets. In further
embodiments, the
terpene or terpenoid compound is menthol (C10H200). Menthol may be synthesised
or it
may be extracted from a plant oil such as the oil of mint.
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[0048] Compositions of the present invention preferably comprise between about
0.5% and
5% of the terpene or terpenoid compound by weight. Preferably, the composition
comprises between about 1% and 4%, between about 1.5% and 3.5%, between about
2%
and 3.5% or, more preferably, about 3% of the terpene or terpenoid compound by
weight.
[0049] Those skilled in the art will understand that a variety of different
alcohols may be used in
accordance with the present invention. In one or more embodiments, the alcohol
is a C1-C6
alcohol and, preferably, a 01-C3 alcohol. The alcohol may, for example, be
ethanol or,
preferably, isopropyl alcohol. The alcohol may be present in the composition
in an amount of
between about 10% and 50% by weight, such as between about 20% and 45% by
weight or
between about 25% and 40% by weight. Preferably, the alcohol is present at a
concentration of
about 35% by weight.
[0050] The composition preferably comprises a surfactant, and in some
embodiments, more
than one surfactant. A surfactant is a surface active agent that can act to
stabilise an emulsion.
Surfactants typically comprise a molecule having a polar or charged,
hydrophilic head group =
and a hydrophobic tail group. Those skilled in the art will understand that
compositions of the
present invention may be formulated using one or more of a variety of
surfactants. The
surfactant may be an ionic, non-ionic or zwitterionic surfactant. Surfactants
suitable for use in
the compositions of the present invention may include anionic, cationic,
amphoteric and non-
ionic surfactants. Non-limiting examples of anionic surfactants include
sulfate esters, sulfonate
esters, phosphate esters and alkyl carboxylates. Non-limiting examples of
cationic surfactants
include quaternary ammonium compounds, such as cetyl trimethylammonium
bromide,
cetylpyridinium chloride, benzethonium chloride and
dioctadecyldimethylammonium bromide.
Non-limiting examples of amphoteric surfactants include betaines, imino
acetates and imino
propionates. Non-limiting examples of non-ionic surfactants include fatty
alcohols, glucosides,
maltosides, polyethoxylated tallow amines, cocoamides, sorbitan alkyl esters,
block copolymers
of polyethylene glycol and polypropylene glycol, ethoxylated amines and
ethoxylated alcohols.
The composition of the present invention may comprise between about 1% and 10%
by weigh
of a surfactant such as between about 3% and 9% by weight or between about 4%
and 8% by
weight of a surfactant.
[0051] In one or more embodiments, the composition of the present invention
comprises
polysorbate 80 and polyethylene glycol 400 (PEG400). Preferably, the
composition comprises
polysorbate 80 at a concentration of between about 0.05% and 1% by weight such
as between
CA 2976564 2017-08-16
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about 0.1% and 0.5% by weight. Preferably, the composition comprises
polysorbate 80 at a
concentration of about 0.2% by weight. The composition may also comprise
PEG400 at a
concentration of between about 1% and 10% by weight such as between about 2%
and 7% by
weight or between about 4% and 6% by weight. Preferably, the composition
comprises
PEG400 at a concentration of about 5% by weight.
[0052] In one embodiment, the composition for treating a skin or mucosal
membrane infection of
the present invention comprises:
glycerol in an amount of between about 30% and 80% by weight;
at least one surfactant in an amount of between about 1% and 10% by weight;
an alcohol in an amount of between about 20% and 60% by weight;
a terpene or terpenoid compound in an amount of between about 0.5% and 5% by
weight; and
a copper compound in an amount of between about 1% and 10% by weight.
[0053] In another embodiment, the composition for treating a skin or mucosal
membrane
infection of the present invention comprises:
glycerol in an amount of between about 30% and 60% by weight;
at least one surfactant in an amount of between about 1% and 10% by weight;
an alcohol in an amount of between about 20% and 50% by weight;
a terpene or terpenoid compound in an amount of between about 0.5% and 10% by
weight; and
a copper compound in an amount of between about 1% and 5% by weight.
[0054] In another embodiment, the composition for treating a skin or mucosal
membrane
infection of the present invention comprises:
glycerol in an amount of at least about 35% by weight;
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at least one surfactant in an amount of between about 1% and 10% by weight;
an alcohol in an amount of between about 10% and 50% by weight;
a terpene or terpenoid compound in an amount of between about 0.5% and 5% by
weight; and
a copper compound in an amount of between about 1% and 5% by weight.
[0055] In another embodiment, the composition comprises:
glycerol in an amount of at least about 40% by weight;
at least one surfactant in an amount of between about 3% and 7% by weight;
an alcohol in an amount of between about 25% and 40% by weight;
a terpene or terpenoid compound in an amount of between about 1% and 4% by
weight;
and
a copper compound in an amount of between about 2% and 4% by weight.
[0056] In a further embodiment, the composition comprises:
glycerol in an amount of at least about 40% by weight;
at least one surfactant in an amount of about 5% by weight;
an alcohol in an amount of about 35% by weight;
a terpene or terpenoid compound in an amount of about 3% by weight; and
a copper compound in an amount of about 3% by weight.
[0057] The composition may further comprise one or more herbal extracts such
as Hypericum
perforatum and/or Calendula officinalis extract. Hypericum perforatum and
Calendula officinalis
extracts have antimicrobial and antiviral activity (Clewell et al. Efficacy
and tolerability
assessment of a topical formulation containing sulfate and Hypericum
perforatum on patients
with herpes skin lesions: a comparative, randomized controlled trial. Journal
of Drugs in
Dermatology 11(2): 209-215; Wolfe et al. Topical application of St. John's
Wort (Hypericum
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perforatum). Planta Med. 80: 109-120; Roveroni-Favaretto et al. Topical
Calendula officinalis L.
successfully treated exfoliative cheilitis: a case report. Cases Journal. 2:
9077) and can be
obtained from various parts of the plant, including flowers, leaves, seeds,
roots and stems. The
extracts can be prepared using distillation, pressing, or solvent (eg,
ethanol) extraction. In one
or more embodiments, the Hypericum perforatum extract is present in the
composition at a
concentration of about 1% by weight or less such as about 0.5% by weight or
less, 0.25% by
weight or less or 0.1% by weight or less. Preferably, the Hypericum perforatum
extract is
present in the composition at a concentration of about 0.05% by weight. In one
or more
embodiments, the Calendula officinalis extract is present in the composition
at a concentration
of about 1% by weight or less such as about 0.5% by weight or less, 0.25% by
weight or less or
0.1% by weight or less. Preferably, the Calendula officinalis extract is
present in the
composition at a concentration of about 0.05% by weight.
[0058] In one embodiment, the composition comprises:
glycerol in an amount of at least about 40% by weight;
at least one surfactant in an amount of about 5% by weight;
an alcohol in an amount of about 35% by weight;
a terpene or terpenoid compound in an amount of about 3% by weight;
a copper compound in an amount of about 3% by weight; and
Hypericum perforatum extract in an amount of between about 0.01% and 2% by
weight.
[0059] In a further embodiment, the composition comprises:
glycerol in an amount of at least about 40% by weight;
at least one surfactant in an amount of about 5% by weight;
an alcohol in an amount of about 35% by weight;
a terpene or terpenoid compound in an amount of about 3% by weight;
a copper compound in an amount of about 3% by weight;
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Hypericum perforatum extract in an amount of between about 0.01% and 2% by
weight;
and
Calendula officinalis extract in an amount of between about 0.01% and 2% by
weight.
[0060] In one or more embodiments, the composition of the present invention
includes
Vitamin E. Vitamin E may be present in, or extracted from, an essential oil.
The vitamin E
is preferably present at a concentration of 1% or less by weight, 0.5% or less
by weight or
0.25% or less by weight. Preferably, the vitamin E is present at a
concentration of about
0.1% by weight.
[0061] In some embodiments, the composition further comprises aloe vera. Aloe
vera is
obtained from plants of the genus Aloe, such as Aloe barbadensis plants. In
one or more
embodiments, the aloe vera is present in the composition at a concentration of
about 1% by
weight or less, about 0.5% or less by weight, about 0.25% or less, about 0.1%
or less by
weight, about 0.05% or less by weight or about 0.025% or less by weight.
Preferably, the
aloe vera is present at a concentration of about 0.01% by weight.
[0062] In one embodiment, the composition comprises:
glycerol in an amount of between about 30% and 80% by weight;
at least one surfactant in an amount between about 1% and 10% by weight;
an alcohol in an amount between about 20% and 60% by weight;
a terpene or terpenoid compound in an amount between about 0.5% and 5% by
weight;
a copper compound in an amount between about 1% and 10% by weight;
Hypericum perforatum extract in an amount of between about 0.01% and 2% by
weight;
Calendula officinalis extract in an amount of between about 0.01% and 2% by
weight;
vitamin E in an amount of between about 0.01% and 2%; and
aloe vera in an amount of between about 0.01% and 2%.
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[0063] The present inventors have surprisingly found that compositions of the
present
invention can be prepared with no, or substantially no, water. Accordingly,
the composition
may be a non-aqueous composition. The compositions were observed to form
stable,
homogenous mixtures. The composition may be stable for at least 3 months, such
as for 6
months, 9 months, 12 months, 15 months, 18 months or 21 months. Preferably,
the
composition is stable for 24 months.
[0064] In one or more embodiments, the composition of the present invention
has a pH of
less than about 7, such as less than about 6, less than about 5, less than
about 4 or less
than about 3. The pH of the composition may be between about 1 and 4 or
between about
1.5 and 3.5. Preferably, the pH of the composition is between about 2 and 2.5.
[0065] In one or more embodiments, the composition of the present invention
has a density
(SG) of between about 0.25 g/mL and 2 g/mL, such as between about 0.5 g/mL and
1.5 g/mL or
between about 0.75 g/mL and 1.25 g/mL. Preferably, the density of the
composition is between
about 1 g/mL and 1.1 g/mL.
[0066] In one or more embodiments, the composition of the present invention
has a
viscosity of between about 100 cps and 500 cps, such as between about 150 cps
and 400
cps or between about 200 cps and 350 cps. Preferably, the viscosity of the
composition is
between about 225 cps and 300 cps.
[0067] The composition may comprise further ingredients that are suitable for
the topical
treatment of skin or mucosal membrane infections. For example, the composition
may further
comprise, inter alia, preservatives, thickeners, osmotic regulators, flavours,
fragrances,
emollients, humectants, colorants pigments or pharmaceutically acceptable
carriers. The
composition may also comprise stabilisers such as propylene glycol which may
be present at a
concentration of between about 5% and 25% by weight or, preferably, between
about 10% and
20% by weight.
[0068] In preferred embodiments, the composition is a homogenous composition.
The
composition is preferably suitable for topical formulation. The composition
may be formulated
as a cream, a lotion, a paste, an emollient, a gel, a foam or an emulsion.
[0069] The term "emulsion" as used herein includes droplets, dispersions or
other structures
that form when two or more immiscible liquids are combined. An emulsion may be
prepared by
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simple stirring and without the use of high shear mixers. Alternatively,
emulsions having smaller
droplet sizes may be prepared using high pressures and/or high shear forces.
Microemulsions
generally comprise droplets having a diameter range from about 1000 nm to
about 500 um.
Nanoemulsions, on the other hand, comprise smaller droplets with a diameter of
less than about
1000 nm.
[0070] The composition may be used to treat a skin or mucosal membrane
infection, and
preferably, a viral infection. The infection may be caused by a poxvirus, a
herpesvirus or a
human papillomavirus. In some embodiments, the viral infection is caused by
herpes simplex
virus, herpes zoster virus, Molluscuum contagiosum, human papillomavirus,
polio virus,
shingles-associated viruses, varicella zoster virus, chicken pox-associated
viruses or human
immunodeficiency virus. Preferably, the viral infection is caused by herpes
simplex virus.
[0071] Those skilled in the art will understand that the compositions of the
present invention are
also useful for treating other skin or mucosal membrane infections. For
example, the
composition may be used to treat a fungal infection, such as tinea. The form
of tinea may be,
for example, tinea pedis, tinea corporis, tinea manuum, tinea cruris, tinea
barbae or tinea
capitis.
[0072] The term "pharmaceutically acceptable" as used herein refers to
substances that do not
cause substantial adverse allergic or immunological reactions when
administered to a subject.
A "pharmaceutically acceptable carrier" includes, but is not limited to,
solvents, coatings,
dispersion agents, wetting agents, isotonic and absorption delaying agents and
disintegrants.
[0073] The term "substantially no" as used in reference to water content means
that water
constitutes less than about 2% by weight such as less than 1% by weight,
preferably less than
0.5% by weight or, more preferably, less than 0.1% by weight.
[0074] The terms "comprise", "comprises", "comprised" or "comprising",
"including" or "having"
and the like in the present specification and claims are used in an inclusive
sense, ie, to specify
the presence of the stated features but not preclude the presence of
additional or further
features.
[0075] In the context of this specification the term "about" is understood to
refer to a range of +/-
10%, preferably +/- 5% or +/- 1% or, more preferably, +/- 0.1%.
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[0076] In the context of this specification the terms "a" and "an" are used
herein to refer to one
or to more than one (i.e to at least one) of the grammatical object of the
article. By way of
example, "an element" means one element or more than one element.
Example 1
[0077] A composition suitable for treating a skin or mucosal membrane
infection was prepared
as set out in Table 1 below.
Table 1
Ingredient %w/w
Glycerol 40
Cupric sulphate pentahydrate 3
Camphor tablets 3
Isopropyl alcohol 35
PEG400 5
Polysorbate 80 0.2
Vitamin E 0.1
Glycerol To 100
Example 2
[0078] A composition suitable for treating a skin or mucosal membrane
infection was prepared
as set out in Table 2 below.
Table 2
Ingredient %wlw
Glycerol 40
Cupric sulphate pentahydrate 3
Aloe Vera 200:1 0.01
Camphor tablets 3
Isopropyl alcohol 35
PEG400 5
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Polysorbate 80 0.2
Vitamin E 0.1
Hypericum perforatum extract 0.05
Calendula officinalis extract 0.05
Glycerol To 100
[0079] In addition to the composition shown in Table 2, compositions
comprising between 1%
and 4% camphor and between 1% and 5% cupric sulphate were also prepared. The
compositions formed a stable, homogenous mixture.
Example 3
[0080] Additional compositions, based on that shown in Table 2, were produced
in which
camphor was replaced with the following alternative terpene/terpenoid
compounds or essential
oils:
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Table 3
Terpenoid/Essential oil %w/w
Menthol 1-4
Tea tree oil 1-4
Eucalyptus oil 1-4
Example 4
[0081] Further compositions suitable for treating a skin or mucosal membrane
infection were
prepared as set out in Table 4.
Table 4
1 2 3 4 5 6 7 8 9
10 11
k
Ingredients /owlw
Glycerol , 40 - 60 42 - 62 44 - 64 46 - 66
48 - 68 49 - 69 , 50 - 70 51 - 72 52 - 72 50 - 70 40 - 60
Copper Salt
(Cupric sulphate 2.5 2.6 2.7 2.8 2.9 3.0 3.1 3.5
3.5 3.6 2.5
pentahydrate)
Camphor 2.5 2.6 2.7 2.8 2.9 3.0 3.1 3.5
3.5 3.6 2.5
Isopropyl alcohol 20 - 45 21 -44 22 - 42 24 -40 26 -
38 25 -37 , 26 - 36 28 - 34 30 - 34 30 - 34 20-45 -
Polysorbate 80 0.1 0,2 0.3 0.4 0.5 0.6 0.2 0.2
0.3 0.2 0.1
Vitamin E 0.1 0.2 0.3 0.4 0.5 0.6 0.4 0.3
0.4 0.3 0.1
_
Calendula
0.01 0.02 0.03 0.04 0.05 0.06 0.04 0.03 0.04
0.03 0.00
officinalis extract .
Aloe vera 0.1 0.2 0.3 0.4 0.5 0.6 0.4 0.4
0.3 0.2 0.00
Hypericum
0.01 0.02 0.03 0.04 0.05 0.06 0.04 . 0.02 0.03
0.02 0.00
perforatum extract
PEG400 1.0 2.0 3.0 4.0 5.0 6.0 5.0 4.0
5.0 6.0 1.0
_
Menthol 0.1 _ 0.2 - 0.1 0.2 - 0.1 0.2
0.3 0.2
Water I Glycerol to 100 to 100 ' to 100 - to 100 to 100
to 100 to 100 ' to 100 to 100 to 100 to 100
[0082] The compositions formed a stable, homogenous mixture.
Example 5 .
[0083] The composition shown in Table 1 was prepared by the following step-
wise process:
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Step 1
Glycerol and cupric sulphate pentahydrate were mixed until completely
dissolved. To
assist dissolution, the mixture was heated to 80 C. If particulate matter was
observed, it
was removed by filtration.
Step 2
Camphor tablets were ground into a powder and dissolved in isopropyl alcohol.
Step 3
PEG400, polysorbate 80 and vitamin E were combined to form a homogenous
mixture.
[0084] The compositions produced by steps 1 to 3 were combined and mixed until
homogenous. Further glycerol was added as appropriate. To avoid isopropyl
alcohol loss, the
final composition was stored in a sealed container at a temperature of below
25 C.
Example 6
(00851 The composition shown in Table 2 was prepared by the following step-
wise process:
Step 1
Glycerol, cupric sulphate pentahydrate and aloe vera were mixed until
completely
dissolved. To assist dissolution, the mixture was heated to 80 C. If
particulate matter
was observed, it was removed by filtration.
Step 2
Camphor tablets were ground into a powder and dissolved in isopropyl alcohol.
Step 3
PEG400, polysorbate 80, vitamin E, Hypericum perforatum extract and Calendula
officinalis extract were combined to form a homogenous mixture.
The compositions produced by steps 1 to 3 were combined and mixed until
homogenous. Further glycerol was added as appropriate. To avoid isopropyl
alcohol
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loss, the final composition was stored in a sealed container at a temperature
of below
25 C.
Example 7
[0086] A composition based on that described in Example 2 was prepared as a 10
kg batch. 0.5
mL aliquots were prepared for stability testing. Each aliquot was stored in a
clear glass vial at
30 C / 65% relative humidity. The composition formed a homogenous mixture with
a pH of
between about 1.5 and 3.5, a density (SG) of between about 1 g/mL and 1.1
g/mL, and a
viscosity of between about 225 cps and 300 cps (S#3, 12 rpm, at 20 C) which
was stable for
more than 12 months.
[0087] Although the invention has been described with reference to specific
embodiments, it will
be appreciated by those skilled in the art that the invention may be embodied
in many other
forms.
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