Note: Descriptions are shown in the official language in which they were submitted.
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COMPOSITIONS AND METHODS FOR
TREATING AND INHIBITING VIRAL INFECTIONS
Technical Field
This invention relates, in general, to compositions and methods for
treating and inhibiting papillomavirus infections and removing warts of
papillomavirus genesis in mammalian hosts, and in particular, to the treatment
and prevention of genital warts and other warts and lesions of the skin and
mucosal surfaces that are associated with infections of the papillomavirus in
mammals. More specifically, this invention relates to compositions and methods
for treating and inhibiting replication of the human papillomarivus, thereby
eliminating the cause of such warts and lesions.
Background of The Invention
The human papillomavirus is a virus of the papillomavirus family that
infects the epidermis of human beings. Such infections may result in
epithelial
lesions or growths, particularly warts, also known as condylomas or
papillomas.
Many different human papillomavirus types have been identified, which are
usually transmitted through skin-to-skin contact (or mucous membrane contact),
including sexual contact. Human papillomavirus types 6 and 11 are most often
associated with unsightly and embarrassing, but usually non-cancerous, warts
on the male genitalia, in and around the vagina, in and around the anus, in
and
around the throat, including the larynx, or other skin and/or mucous membrane
areas. Other human papillomavirus types include, but are not limited to, types
16 and 18, which are also transmitted through skin-to-skin contact (or mucous
membrane contact), including sexual contact, and are associated with unsightly
and often embarrassing anogenital warts. The human papillomavirus is also
known generally to play a role in, and may in fact lead to, several types of
cancers, including cervical, vaginal, vulvar, penile, anal, rectal and/or
oropharyngeal cancers, although types 16 and 18 are associated with a higher
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risk of cancer than types 6 and 11 and other types. Other human papillomavirus
types include type 1, which is associated with unsightly but usually non-
cancerous warts that appear on the feet. The present invention may be used to
treat and inhibit infections caused by all of the aforementioned human
papillomavirus types, but the invention is not limited to the treatment and
inhibition of infections caused solely by the human papillomavirus types
mentioned above.
Infections caused by the human papillomavirus. and warts associated with
that virus, have often been treated and/or removed using one of the following
compositions and/or methods: cryotherapy, which involves freezing the abnormal
cells with liquid nitrogen; conization, or a Gone biopsy, which removes the
abnormal areas surgically; or Loop Electrosurgical Excision Procedure (LEEP),
where the abnormal cells are removed with an electrical current. For warts in
less sensitive areas, acids may be applied to assist in terminating the wart;
canadid antigen may be injected to stimulate the immune system to fight off
the
wart; a topical medication called imiquimod may be applied; or no treatment at
all may be used, which implies simply waiting to see if the cells can heal on
their
own.
However, many of these compositions and/or methods include burning or
freezing away the wart (using chemicals or an electrical current), which can
often
be a painful process, and in any event can leave unsightly scarring. Others
utilize
a medication that modifies the immune response to the virus in order to treat
the
wart, but these often require more time to fight the virus and terminate the
wart,
which does not always happen. Additionally, while these methods may be used
to target and treat existing warts, they do not necessarily treat the
underlying
virus which may result in a recurrence of the warts, as the warts are a
manifestation of the viral infection.
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It is therefore one of the primary objects of the present invention to
provide compositions and methods for treating infections caused by the human
papillomavirus and for removing warts associated with that virus,
particularly, but
not limited to, those associated with types 1, 6, 11, 16 and 18
Another object of the present invention is to provide compositions and
methods for treating infections caused by the human papillomavirus and for
removing warts associated with that virus in which the compositions are safe
enough to be used topically on highly sensitive regions of the skin, such as
may
be found in the genital areas.
Still another object of the present invention is to provide compositions and
methods for treating infections caused by the human papillomavirus and for
removing warts associated with that virus which can be administered to humans
through different routes of administration and in a variety of forms.
Yet another object of the present invention is to provide compositions and
methods for treating infections caused by the human papillomavirus and for
removing warts associated with that virus which can also be used to cover
scars
left after conventional surgical removal of such warts, in order to prevent re-
growth of such warts.
Still one other object of the present invention is to provide compositions
and methods for treating infections caused by the human papillomavirus and for
removing warts associated with that virus which provide quick relief and
termination of the wart, as well as sustained relief to prevent additional
warts
from forming, by inhibiting replication of virus.
Summary of the invention
The present invention provides compositions and methods for treating an
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infection associated with the human papillomavirus: such an infection may be
manifested in a human as epithelial lesions, including warts, and particularly
skin
warts, lesions and anogenital warts. The compositions of the invention for
treating and removing such warts comprise at least one compound selected from
the group consisting of chloroquine, hydroxychloroquine and amothaquine. More
particularly, the compositions comprise either chloroquine alone or
hydroxychloroquine alone or amodiaquine alone, or pharmaceutically acceptable
salts thereof, as the active ingredient, or combinations of any two, or all
three,
of those compounds, or pharmaceutically acceptable salts thereof, as the
active
ingredients. Optionally, the
compositions may also comprise suitable
pharmaceutically acceptable carriers, excipients and/or adjuvants, and/or
other
non-active ingredients, such as ethyl alcohol, lidocaine, epinephrine and/or
diphenhydramine. It is believed that the compositions of the invention act by
inhibiting replication of human papillomavirus which causes such warts.
The methods of the invention comprise administering a pharmaceutical
composition comprising at least one compound selected from the group
consisting of chloroquine. hydroxychloroquine, amodiaquine and
pharmaceutically acceptable salts thereof, to a human being, using one or more
routes of administration that are well known in the art. At present, the
following
are the preferred routes of administration_ topical (epicutaneous), in forms
such
as a gel, cream, spray, soap or other bathing apparatus; transdermal, in the
form
of a patch; transmucosal (also known as pharmaceutical pessary delivery)
through the vagina or rectum, in the form, for example, of an ovule or
suppository, respectively; nasal, such as delivery by inhalation of aerosol
droplets produced, for example, with the aid of a nebulizen and infusion under
the skin in the form of an injection Other routes
for administering
pharmaceutical compositions according to the invention are possible.
Thus_ one aspect of the present invention generally concerns methods for
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the treatment of a human or mammalian subject suffering from an existing
papillomavirus infection by inhibiting further replication of the virus. In
one
embodiment of this aspect, the methods comprise administering a
therapeutically effective amount of chloroquine or a pharmaceutically
acceptable
salt thereof to the subject. In another embodiment the methods comprise
administering a therapeutically effective amount of hydroxychloroquine or a
pharmaceutically acceptable salt thereof to the subject. In yet another
embodiment the methods comprise administering a therapeutically effective
amount of amodiaquine or a pharmaceutically acceptable salt thereof to the
subject. In still another embodiment of this aspect of the invention, the
methods
comprise administering a therapeutically effective amount of chloroquine or a
pharmaceutically acceptable salt thereof together with a therapeutically
effective
amount of hydroxychloroquine or a pharmaceutically acceptable salt thereof to
the subject In yet another embodiment, the methods comprise administering
a therapeutically effective amount of chloroquine or a pharmaceutically
acceptable salt thereof together with a therapeutically effective amount of
amodiaquine or a pharmaceutically acceptable salt thereof to the subject. In
still
another embodiment, the methods comprise administering a therapeutically
effective amount of hydroxychloroquine or a pharmaceutically acceptable salt
thereof together with a therapeutically effective amount of amodiaquine or a
pharmaceutically acceptable salt thereof to the subject. In yet another
embodiment, the methods comprise administering a therapeutically effective
amount of chloroquine or a pharmaceutically acceptable salt thereof together
with a therapeutically effective amount of hydroxychioroquine or a
pharmaceutically acceptable salt thereof and a therapeutically effective
amount
of amodiaquine or a pharmaceutically acceptable salt thereof to the subject.
Another aspect of the invention generally concerns methods for the
prevention or inhibition of the development or recurrence of the development
in
a human or mammalian subject of an infection of the human papillomavirus by
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inhibiting replication of the virus. In one embodiment of this aspect, the
methods
comprise administering an antivirally effective amount of chloroquine or a
pharmaceutically acceptable salt thereof to the subject. In another embodiment
the methods comprise administering an antivirally effective amount of
hydroxychloroquine or a pharmaceutically acceptable salt thereof to the
subject.
In still anther embodiment the methods comprise administering an antivirally
effective amount of amodiaquine or a pharmaceutically acceptable salt thereof
to the subject. In still another embodiment of this aspect of the invention,
the
methods comprise administering an antivirally effective amount of chloroquine
or a pharmaceutically acceptable salt thereof together with an antivirally
effective
amount of hydroxychloroquine or a pharmaceutically acceptable salt thereof to
the subject. In yet another embodiment, the methods comprise administering
an antivirally effective amount of chloroquine or a pharmaceutically
acceptable
salt thereof together with an anitvirally effective amount of amodiaquine or a
pharmaceutically acceptable salt thereof to the subject. In still another
embodiment, the methods comprise administering an antivirally effective amount
of hydroxychloroquine or a pharmaceutically acceptable salt thereof together
with an antivirally effective amount of amodiaquine or a pharmaceutically
acceptable salt thereof to the subject. In yet another embodiment, the methods
comprise administering an antivirally effective amount of chloroquine or a
pharmaceutically acceptable salt thereof together with an antivirally
effective
amount of hydroxychloroquine or a pharmaceutically acceptable salt thereof and
an anitvirally effective amount of amodiaquine or a pharmaceutically
acceptable
salt thereof to the subject.
Another aspect of the invention generally concerns pharmaceutical
compositions for the treatment of a papillomavirus infection in a human or
mammalian host by inhibiting replication of the virus. In one embodiment of
this
aspect, the compositions comprise a therapeutically effective amount of
chloroquine or a pharmaceutically acceptable salt thereof. In another
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embodiment the compositions comprise a therapeutically effective amount of
hydroxychloroguine or a pharmaceutically acceptable salt thereof. In still
another embodiment the compositions comprise a therapeutically effective
amount of amodiaguine or a pharmaceutically acceptable salt thereof. In still
another embodiment of this aspect of the invention, the compositions comprise
a therapeutically effective amount of chloroguine or a pharmaceutically
acceptable salt thereof together with a therapeutically effective amount of
hydroxychloroguine or a pharmaceutically acceptable salt thereof. In yet
another
embodiment, the compositions comprise a therapeutically effective amount of
chloroguine or a pharmaceutically acceptable salt thereof together with a
therapeutically effective amount of amodiaquine or a pharmaceutically
acceptable salt thereof. In still another embodiment, the compositions
comprise
a therapeutically effective amount of hydroxychloroguine or a pharmaceutically
acceptable salt thereof together with a therapeutically effective amount of
amodiaguine or a pharmaceutically acceptable salt thereof. In yet another
embodiment, the compositions comprise a therapeutically effective amount of
chloroguine or a pharmaceutically acceptable salt thereof together with a
therapeutically effective amount of hydroxychloroguine or a pharmaceutically
acceptable salt thereof and a therapeutically effective amount of amodiaguine
or a pharmaceutically acceptable salt thereof.
Another aspect of the invention generally concerns methods for the
treatment of a papillomavirus infection in a cell of human or mammalian
origin,
as well as methods of inhibiting the replication of a papillomavirus in a cell
of
human or mammalian origin infected with such a virus. In one embodiment of
this aspect, the methods comprise exposing the cell to an antivirally
effective
amount of chloroguine or a pharmaceutically acceptable salt thereof. in
another
embodiment the methods comprise exposing the cell to an antivirally effective
amount of hydroxychloroguine or a pharmaceutically acceptable salt thereof. In
yet another embodiment the methods comprise exposing the cell to an
antivirally
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effective amount of amodiaquine or a pharmaceutically acceptable salt thereof.
In still another embodiment of this aspect of the invention, the methods
comprise
exposing the cell to an antivirally effective amount of chloroquine or a
pharmaceutically acceptable salt thereof together with an antivirally
effective
amount of hydroxychloroquine or a pharmaceutically acceptable salt thereof. In
yet another embodiment, the methods comprise exposing the cell to an
antivirally effective amount of chloroquine or a pharmaceutically acceptable
salt
thereof together with an antivirally effective amount of amodiaquine or a
pharmaceutically acceptable salt thereof. In still another embodiment, the
methods comprise exposing the cell to an antivirally effective amount of
hydroxychloroquine or a pharmaceutically acceptable salt thereof together with
an antivirally effective amount of amodiaquine or a pharmaceutically
acceptable
salt thereof. In yet another embodiment, the methods comprise exposing the
cell to an antivirally effective amount of chloroquine or a pharmaceutically
acceptable salt thereof together with an antivirally effective amount of
hydroxychloroquine or a pharmaceutically acceptable salt thereof and an
antivirally effective amount of amodiaquine or a pharmaceutically acceptable
salt
thereof.
These and other aspects, features, objects and advantages of the present
invention will become more apparent to those skilled in the art from the
following
detailed description of the presently most preferred embodiments thereof.
Detailed Description of The Preferred Embodiment
The present invention resides in the discovery that the known compounds
chloroquine, hydroxychloroquine and amodiaquine, or pharmaceutically
acceptable salts thereof, all of which have been used previously as
antimalarial
agents and/or to treat disorders of the immune system, also have utility in
treating infections of the human and other mammalian papillomaviruses, and in
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particular, in treating and in inhibiting replication of such viruses and in
removing
the warts associated with such infections, as well as in preventing the
recurrence
of such warts.
The molecular structures of chloroquine, hydroxychloroquine and
amodiaquine are provided below, as Formula (I), Formula (II) and Formula
(Ill),
respectively.
I
Cf. Formula (I)
OH
1
c,,-- Formula (II)
1
HN -
-
= v.--
C I N Formula (Ill)
As is known, and as can be seen in the structural formulas set out above,
these three compounds are related to one another in that their structures have
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a heterodicyclic portion in common, namely, the 7-chloro derivative of the 4-
aminoquinoline moiety. Chloroquine (Formula 1) has been marketed under the
brand name Resochin, while hydroxychloroquine (Formula II) has been marketed
under the brand name Plaquenil, and amodiaquine (Formula III) has been
marketed under the brand name Camoquin. Chloroquine is commercially
available as the pharmaceutically acceptable salt chloroquine phosphate, and
may be purchased in solid (tablet) form from a wide variety of sources such as
Ohm Laboratories. Inc. of North Brunswick, NJ, U.S.A., while a ready-made
aqueous solution may be purchased from a wide variety of sources, including
Sai Parenterals (P) Ltd., of Hyserabad, India. or Scott Edil Pharmacia Ltd.,
of
Jhannajd. India. Hydroxychloroquine, in solid (tablet) form, is commercially
available as the pharmaceutically acceptable salt hydroxychloroquine sulphate,
and may be purchased from a wide variety of sources such as West-Ward
Pharmaceutical Corporation of Eatontown, NJ, U.S.A. Amodiaquine, in solid
(tablet) form, is commercially available as the pharmaceutically acceptable
salt
amodiaquine hydrochloride, and may be purchased from a wide variety of
sources, including Parke, Davis & Company, a division of Pfizer Inc.,
headquartered in New York, NY, U.S.A.
In the preferred embodiments, the compositions of the invention comprise
either chloroquine (Formula I) alone or hydroxychloroquine (Formula II) alone
or
amodiaquine (Formula 111) alone as the active ingredient, or either
chloroquine
combined with hydroxychloroquine, or chloroquine combined with arnodiaquine,
or hydroxychloroquine combined with amodiaquine, or chloroquine combined
with both hydroxychloroquine and amodiaquine, as the active ingredients. In
general, as mentioned above and as set forth in further detail below, the
methods of the invention comprise, in the preferred embodiments, administering
the pharmaceutical compositions of the invention comprising the active
ingredient or ingredients to a mammal such as a human being using one or more
of the preferred routes of administration, which include direct topical
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(epicutaneous) administration, in forms such as gel, cream, lotion, solution,
spray, soap or other bathing apparatus; transdermal administration, in the
form
of a patch; transmucosal administration (also known as pharmaceutical pessary
delivery) through the vagina or rectum, in the form, for example, of an ovule
or
a suppository, respectively: respiratory administration, such as delivery via
inhalation through the nostrils and nasal passages of aerosol droplets
produced,
for example, with the aid of a nebulizer; and infusion under the skin in the
form
of an intra-epidermal injection.
Although the compositions and methods of the invention will be
illustratively described hereinafter with reference to topical, transdermal
and
infusional routes of administration, it should be understood that the
invention is
not limited to the specific cases described, but extends also to the use of
other
compatible routes for administering pharmaceutical compositions according to
the invention, as will be evident to those skilled in the art, including but
not
limited to other topical and/or parenteral routes, such as buccal,
conjunctival,
endotracheal, intramuscular, intravascular, laryngeal, or ophthalmic. or even
enteral (oral) routes, any one or more of which may ultimately be found to be
more preferable. Suitable formulations for any route of administration that is
ultimately selected are known and are described in well-known texts, including
for example Remington, The Science and Practice of Pharmacy, 21 edition,
2005, Mack Publishing Company, Easton, PA. and therefore such formulations
may easily be prepared by those of ordinary skill in the art.
It is well understood, however, that proper dosages of any medication
may vary from one individual to another, depending on many factors such as the
intensity of the affliction and the selected route of administration, as well
as the
weight, age and gender of the patient. Therefore, the effective dosages of the
pharmaceutical compositions of the present invention should be determined by
a specialist in this matter, such as a medical doctor or other health care
provider,
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depending on these and other parameters. Nevertheless, for the sake of
illustration only, exemplary formulations, preparation procedures and dosages,
for topical, transdermal and infusional routes of administration, are provided
below for the sake of guidance.
When the compositions of the invention comprising chloroquine as the
only active ingredient are to be administered topically (epicutaneously), in
the
form of either a gel or a spray, the compositions preferably comprise
chloroquine
plus optional non-active ingredients. The non-active ingredients may comprise
ethyl alcohol and peppermint spirit oil, and the gel form may additionally
comprise lidocaine jelly or ointment, while the spray form may additionally
comprise lidocaine as a 2% solution. All of the non-active ingredients are
conventional and are available commercially from a wide variety of sources.
The
non-active ingredients are exemplary only, but are included for the following
purposes: the lidocaine functions as an analgesic, the ethyl alcohol functions
as
an antiseptic, while the peppermint spirit oil functions to provide a pleasing
odor,
A particularly preferred composition for the gel form may be prepared from the
starting ingredients set forth below:
Chloroquine phosphate 4000 mg (8 500-mg tablets)
Lidocaine jelly 2% or ointment 5% 10 ml or 10 mg, respectively
Ethyl alcohol (70% aqueous solution) 15 ml
Peppermint spirit oil 2.5 ml
Water 2.5 ml
Preferably, this composition is prepared by crushing the chloroquine
phosphate tablets in a mortar. and then adding each of the non-active
ingredients, in the sequence listed above, sufficient to make a total of
approximately 30 gm of the gel or spray. The gel form may then be transferred
to a tube or other appropriate container, while the spray form may then be
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transferred into a conventional spray bottle.
The gel form of this medication is preferably administered to a patient as
follows. The affected areas are first cleaned with one or more alcohol swabs,
and optionally, each wart to be treated may then be filed lightly for
approximately
30 seconds with a conventional nail filing device or instrument (which can be
purchased from a variety of sources, including beauty supply shops); only
warts
that appear on the toes, fingers, elbows, knees and other hard surfaces of the
patient's skin should be filed, whereas warts appearing on soft tissues, such
as
the genitalia or in the oral cavity, need not (and should not) be filed. This
filing,
although optional, is preferred since such filing accelerates removal of the
wart(s) by improving the contact between the wart and the medication.
Thereafter, an amount of the gel approximately equal to the surface area of
each
wart (or an amount equal to the surface area of the tip of a finger) is
applied to
the affected area, after which that area may optionally be covered with a
sterile
bandage. The gel form is preferably administered to the patient in the
foregoing
manner once or twice a day, for approximately one to four weeks, until
disappearance of the wart(s). The spray form of this medication is preferably
administered to a patient in the same manner, although the dosage is
preferably
two puffs applied to the affected areas once or twice daily.
When the compositions of the invention comprising chloroquine as the
only active ingredient are to be administered transdermally, in the form of a
patch, approximately 3.5 gm of the gel form (prepared as described above) may
be transferred to the pad of a conventional 3.5 mini-patch. This form of the
medication is preferably administered to a patient in the same manner as the
gel
form, although the dosage for the patch form preferably constitutes applying a
patch to each affected area once a day, and replacing it with a fresh patch
once
every 24 hours (approximately), until disappearance of the wart(s). It is to
be
understood that the patch form can also be used to cover the scars left after
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conventional surgical removal of a wart, with replacement every other day, in
order to prevent re-growth of the wart.
When the compositions of the invention comprising chloroquine as the
only active ingredient are to be administered in injectable form, the
compositions
preferably comprise an aqueous solution of chloroquine plus optional non-
active
ingredients. The non-active ingredients may comprise diphenhydramine,
lidocaine solution and epinephrine. A particularly preferred composition is
set
forth below:
Chloroquine phosphate solution 20 ml
Lidocaine (2% solution) 5 ml
Epinephrine Injection 1:1000 2.5 ml
Diphenhydramine 50 mgirril 2.5 ml
Each milliliter of the chloroquine phosphate solution contains 64.5 mg
B.P. (British Pharmacopia) of chloroquine phosphate, which is equivalent to 40
mg of chloroquine. All of the non-active ingredients are conventional and are
available commercially from a wide variety of sources. The non-active
ingredients are included for the following purposes: the lidocaine functions
as a
local anaesthetic, the diphenhydramine functions as an antihistimine to
decrease
any possible allergic reaction to the active ingredient, while the epinephrine
functions to constrict small blood vessels. Preferably, this composition is
prepared by mixing the active ingredient with the non-active ingredients (in
any
sequence), so as to yield a sufficient amount of the injectable form of the
medication to fill a 30 ml vial.
The injectable form of this medication is preferably administered to a
patient as follows. Tuberculin syringes, each having a capacity of 3 ml to 5
ml,
are used to withdraw aliquots of 0.5 ml to 1 ml from the 30 ml vial. This
amount
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is then injected (with appropriate sterilization) into or beneath the base of
each
wart or infected area, once a day for 5-7 days, until disappearance of the
wart(s)
or infection. Although administration by injection is the fastest-acting route
of
administration for the medication, it is the preferred route of administration
only
for wafts or infections appearing in one or more body cavities or on the hard
surfaces of the skin, such as the toes or other parts of the foot, the fingers
or
other parts of the hand, the elbows and the knees: it is not the preferred
route
of administration for warts appearing on the male genitalia. Further, although
the
preparation of an injectable form has been described above only with respect
to
compositions of the invention comprising chloroquine as the sole active
ingredient, those of ordinary skill in the art will be capable of formulating
injectable forms of the other compositions of the invention described below,
including those comprising hydroxychloroquine alone or amodiaquine alone, and
including those comprising more than one of the three active ingredients.
When the compositions of the invention comprising hydroxychloroquine
as the only active ingredient are to be administered topically
(epicutaneously).
in the form of either a gel or a spray, the compositions preferably comprise
hydroxychioroquine plus optional non-active ingredients. As above, the non-
active ingredients may comprise ethyl alcohol and peppermint spirit oil, and
the
gel form may additionally comprise lidocaine jelly or ointment, while the
spray
form may additionally comprise lidocaine as a 2% solution. A particularly
preferred composition for the gel form may be prepared from the starting
ingredients set forth below:
Hydroxychloroquine sulphate 2400 mg (12 200-mg tablets)
Lidocaine jelly 2% or ointment 5% 10 ml or 10 mg, respectively
Ethyl alcohol (70% aqueous solution) 15 ml
Peppermint spirit oil 2.5 ml
Water 2.5 ml
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Preferably, this composition is prepared by crushing the
hydroxychloroquine sulphate tablets in a mortar, and then adding each of the
non-active ingredients, in the sequence listed above, sufficient to make a
total
of about 30 gm of the gel or spray. The gel form may then be transferred to a
tube or other appropriate container, while the spray form may then be
transferred
into a conventional spray bottle.
The gel form of this medication is preferably administered to a patient
topically as follows. The affected areas are first cleaned with one or more
alcohol swabs, and optionally, each wart to be treated may then be filed for
approximately 30 seconds with a conventional nail filing device or instrument
(which can be purchased from a variety of sources, including beauty supply
shops); only warts that appear on the toes, fingers, elbows, knees and other
hard surfaces of the patient's skin should be filed, whereas warts appearing
on
soft tissues, such as the genitalia or in the oral cavity, need not (and
should not)
be filed. This filing, although optional, is preferred since such filing
accelerates
removal of the wart(s). Thereafter, an amount of the gel approximately equal
to
the surface area of each wart (or an amount equal to the surface area of the
tip
of a finger) is applied to the affected area, after which that area may
optionally
be covered with a sterile bandage. The gel form is preferably administered to
the patient in the foregoing manner once or twice a day, for approximately one
to four weeks, until disappearance of the wart(s). The spray form of this
medication is preferably administered to a patient in the same manner,
although
the dosage for the spray form is preferably two puffs applied to the affected
areas once or twice daily.
When the compositions of the invention comprising hydroxychloroquine
as the only active ingredient are to be administered transdermally, in the
form of
a patch, approximately 3.5 gm of the gel form (prepared as described above)
may be transferred to the pad of a conventional 3.5 mini-patch. This form of
the
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medication is preferably administered to a patient in the same manner as the
gel
form, although the dosage for the patch form preferably constitutes applying a
patch to each affected area once a day, and replacing it with a fresh patch
once
every 24 hours (approximately), until disappearance of the wart(s). It is to
be
understood that the patch form can also be used to cover the scars left after
conventional surgical removal of a wart, with replacement every other day, in
order to prevent re-growth of the wart.
When the compositions of the invention comprising amodiaquine as the
only active ingredient are to be administered topically (epicutaneously), in
the
form of either a gel or a spray, the compositions preferably comprise
amodiaquine plus optional non-active ingredients. As above, the non-active
ingredients may comprise ethyl alcohol and peppermint spirit oil, and the gel
form may additionally comprise lidocaine jelly or ointment, while the spray
form
may additionally comprise lidocaine as a 2% solution. A particularly preferred
composition for the gel form is set forth below:
Amodiaquine hydrochloride 800 mg (4 200-mg tablets)
Lidocaine jelly 2% or ointment 5% 10 ml or 10 gm, respectively
Ethyl alcohol (70% aqueous solution) 15 ml
Peppermint spirit oil 2.5 ml
Water 2.5 ml
Preferably, this composition is prepared by crushing the amodiaquine
hydrochloride tablets in a mortar, and then adding each of the non-active
ingredients, in the sequence listed above, sufficient to make a total of
approximately 30 gm of the gel or spray. The gel form may then be transferred
to a tube or other appropriate container, while the spray form may then be
transferred into a conventional spray bottle.
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The gel form of this medication is preferably administered to a patient as
follows. The affected areas are first cleaned with one or more alcohol swabs,
and optionally, each wart to be treated may then be filed lightly for
approximately
30 seconds with a conventional nail filing device or instrument (which can be
purchased from a variety of sources, including beauty supply shops); only
warts
that appear on the toes, fingers, elbows, knees and other hard surfaces of the
patient's skin should be filed, whereas warts appearing on soft tissues, such
as
the genitalia or in the oral cavity, need not (and should not) be filed. This
filing,
although optional, is preferred since such filing accelerates removal of the
wart(s) by improving the contact between the wart and the medication.
Thereafter, an amount of the gel approximately equal to the surface area of
each
wart (or an amount equal to the surface area of the tip of a finger) is
applied to
the affected area, after which that area may optionally be covered with a
sterile
bandage. The gel form is preferably administered to the patient in the
foregoing
manner once or twice a day, for approximately one to four weeks, until
disappearance of the wart(s). The spray form of this medication is preferably
administered to a patient in the same manner, although the dosage is
preferably
two puffs applied to the affected areas once or twice daily.
When the compositions of the invention comprising amodiaquine as the
only active ingredient are to be administered transdermally, in the form of a
patch. approximately 3.5 gm of the gel form (prepared as described above) may
be transferred to the pad of a conventional 3.5 mini-patch. This form of the
medication is preferably administered to a patient in the same manner as the
gel
form, although the dosage for the patch form preferably constitutes applying a
patch to each affected area once a day, and replacing it with a fresh patch
once
every 24 hours (approximately), until disappearance of the wart(s). It is to
be
understood that the patch form can also be used to cover the scars left after
conventional surgical removal of a wart, with replacement every other day, in
order to prevent re-growth of the wart.
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When the compositions of the invention comprising chloroquine in
combination with hydroxychloroquine as the active ingredients are to be
administered topically (epicutaneously), in the form of either a gel or a
spray, the
compositions preferably comprise chloroquine and hydroxychloroquine plus
optional non-active ingredients. As above, the non-active ingredients may
comprise ethyl alcohol and peppermint spirit oil, and the gel form may
additionally comprise lidocaine jelly or ointment, while the spray form may
additionally comprise lidocaine as a 2% solution. A particularly preferred
composition for the gel form is set forth below:
Chloroquine phosphate 4000 mg (8 500-mg tablets)
Hydroxychloroquine sulfate 2400 mg (12 200-mg tablets)
Lidocaine jelly 2% or ointment 5% 10 ml or 10 gm, respectively
Ethyl alcohol (70% aqueous solution) 15 ml
Peppermint spirit oil 2.5 ml
Water 2.5 ml
Preferably, this composition is prepared by crushing the chloroquine
phosphate tablets together with the hydroxychloroquine sulfate tablets in a
mortar, and then adding each of the non-active ingredients, in the sequence
listed above, sufficient to make a total of about 30 gm of the gel or spray.
The
gel form may then be transferred to a tube or other appropriate container,
while
the spray form may then be transferred into a conventional spray bottle.
The gel form of this medication is preferably administered to a patient as
follows. The affected areas are first cleaned with one or more alcohol swabs,
and optionally, each wart to be treated may then be filed for approximately 30
seconds with a conventional nail filing device or instrument (which can be
purchased from a variety of sources, including beauty supply shops); only
warts
that appear on the toes, fingers, elbows, knees and other hard surfaces of the
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patients skin should be filed, whereas warts appearing on soft tissues, such
as
the genitalia or in the oral cavity, need not (and should not) be filed. This
filing.
although optional, is preferred since such filing accelerates removal of the
wart(s) Thereafter, an amount of the gel approximately equal to the surface
area
of each wart (or an amount equal to the surface area of the tip of a finger)
is
applied to the affected area, after which that area may optionally be covered
with
a sterile bandage. The gel form is preferably administered to the patient in
the
foregoing manner once or twice a day, for approximately one to four weeks,
until
disappearance of the wart(s). The spray form of this medication is preferably
administered to a patient in the same manner, although the dosage is
preferably
two puffs applied to the affected areas once or twice daily.
When the compositions of the invention comprising chloroquine in
combination with hydroxychloroquine as the active ingredients are to be
administered transdermally, in the form of a patch, approximately 3.5 gm of
the
gel form (prepared as described above) may be transferred to the pad of a
conventional 3.5 mini-patch. This form of the medication is preferably
administered to a patient in the same manner as the gel form, although the
dosage for the patch form preferably constitutes applying a patch to each
affected area once a day, and replacing it with a fresh patch once every 24
hours
(approximately), until disappearance of the wart(s) It is to be understood
that
the patch form can also be used to cover the scars left after conventional
surgical removal of a wart, with replacement every other day, in order to
prevent
re-growth of the wart.
When the compositions of the invention comprising chloroquine in
combination with amodiaquine as the active ingredients are to be administered
topically (epicutaneously), in the form of either a gel or a spray, the
compositions
preferably comprise chloroquine and amodiaquine plus optional non-active
ingredients. As above, the non-active ingredients may comprise ethyl alcohol
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and peppermint spirit oil, and the gel form may additionally comprise
lidocaine
jelly or ointment, while the spray form may additionally comprise lidocaine as
a
2% solution. A particularly preferred composition for the gel form may be
prepared from the starting ingredients set forth below:
Chloroquine phosphate 4000 mg (8 500-mg tablets)
Amocliaquine hydrochloride 800 mg (4 200-mg tablets)
Lidocaine jelly 2% or ointment 5% 10 ml or 10 mg, respectively
Ethyl alcohol (70% aqueous solution) 15 ml
Peppermint spirit oil 2.5 ml
Water 2.5 ml
Preferably, this composition is prepared by crushing the chloroquine
phosphate tablets together with the amodiaquirie hydrochloride tablets in a
mortar, and then adding each of the non-active ingredients, in the sequence
listed above, sufficient to make a total of about 30 gm of the gel or spray.
The
gel form may then be transferred to a tube or other appropriate container,
while
the spray form may then be transferred into a conventional spray bottle_
The gel form of this medication is preferably administered to a patient as
follows. The affected areas are first cleaned with one or more alcohol swabs,
and optionally, each wart to be treated may then be filed for approximately 30
seconds with a conventional nail filing device or instrument (which can be
purchased from a variety of sources, including beauty supply shops); only
warts
that appear on the toes, fingers, elbows, knees and other hard surfaces of the
patient's skin should be filed, whereas warts appearing on soft tissues, such
as
the genitalia or in the oral cavity, need not (and should not) be filed. This
filing,
although optional, is preferred since such filing accelerates removal of the
wart(s) Thereafter, an amount of the gel approximately equal to the surface
area
of each wart (or an amount equal to the surface area of the tip of a finger)
is
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applied to the affected area, after which that area may optionally be covered
with
a sterile bandage. The gel form is preferably administered to the patient in
the
foregoing manner once or twice a day, for approximately one to four weeks,
until
disappearance of the wart(s). The spray form of this medication is preferably
administered to a patient in the same manner, although the dosage is
preferably
two puffs applied to the affected areas once or twice daily.
When the compositions of the invention comprising chloroquine in
combination with amodiaquine as the active ingredients are to be administered
transdermally, in the form of a patch, approximately 3.5 gm of the gel form
(prepared as described above) may be transferred to the pad of a conventional
3.5 mini-patch. This form of the medication is preferably administered to a
patient in the same manner as the gel form, although the dosage for the patch
form preferably constitutes applying a patch to each affected area once a day,
and replacing it with a fresh patch once every 24 hours (approximately). until
disappearance of the wart(s). It is to be understood that the patch form can
also
be used to cover the scars left after conventional surgical removal of a wart,
with
replacement every other day, in order to prevent re-growth of the wart.
When the compositions of the invention comprising hydroxychloroquine
in combination with amodiaquine as the active ingredients are to be
administered
topically (epicutaneously), in the form of either a gel or a spray, the
compositions
preferably comprise hydroxychloroquine and amodiaquine plus optional non-
active ingredients. As above, the non-active ingredients may comprise ethyl
alcohol and peppermint spirit oil, and the gel form may additionally comprise
lidocaine jelly or ointment, while the spray form may additionally comprise
lidocaine as a 2% solution. A particularly preferred composition for the gel
form
may be prepared from the starting ingredients set forth below:
Hydroxychloroquine sulphate 2400 mg (12 200-mg tablets)
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Amodiaquine hydrochloride 800 mg (4 200-mg tablets)
Lidocaine jelly 2% or ointment 5% 10 ml or 10 mg, respectively
Ethyl alcohol (70% aqueous solution) 15 ml
Peppermint spirit oil 2.5 ml
Water 2.5 ml
Preferably, this composition is prepared by crushing the
hydroxychloroquine sulphate tablets together with the amodiaquine
hydrochloride tablets in a mortar, and then adding each of the non-active
ingredients, in the sequence listed above, sufficient to make a total of about
30
grn of the gel or spray. The gel form may then be transferred to a tube or
other
appropriate container, while the spray form may then be transferred into a
conventional spray bottle.
The gel form of this medication is preferably administered to a patient as
follows. The affected areas are first cleaned with one or more alcohol swabs,
and optionally, each wart to be treated may then be filed for approximately 30
seconds with a conventional nail filing device or instrument (which can be
purchased from a variety of sources, including beauty supply shops): only
warts
that appear on the toes, fingers, elbows, knees and other hard surfaces of the
patient's skin should be filed, whereas warts appearing on soft tissues, such
as
the genitalia or in the oral cavity, need not (and should not) be filed This
filing,
although optional, is preferred since such filing accelerates removal of the
wart(s) Thereafter, an amount of the gel approximately equal to the surface
area
of each wart (or an amount equal to the surface area of the tip of a finger)
is
applied to the affected area, after which that area may optionally be covered
with
a sterile bandage. The gel form is preferably administered to the patient in
the
foregoing manner once or twice a day, for approximately one to four weeks.
until
disappearance of the wart(s). The spray form of this medication is preferably
administered to a patient in the same manner, although the dosage is
preferably
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two puffs applied to the affected areas once or twice daily.
When the compositions of the invention comprising hydroxychloroquine
in combination with amodiaquine as the active ingredients are to be
administered
transdermally, in the form of a patch, approximately 3.5 gm of the gel form
(prepared as described above) may be transferred to the pad of a conventional
3.5 mini-patch. This form of the medication is preferably administered to a
patient in the same manner as the gel form, although the dosage for the patch
form preferably constitutes applying a patch to each affected area once a day,
and replacing it with a fresh patch once every 24 hours (approximately), until
disappearance of the wart(s). It is to be understood that the patch form can
also
be used to cover the scars left after conventional surgical removal of a wart,
with
replacement every other day, in order to prevent re-growth of the wart.
When the compositions of the invention comprising chloroquine in
combination with both hydroxychloroquine and amodiaquine as the active
ingredients are to be administered topically (epicutaneously), in the form of
either
a gel or a spray, the compositions preferably comprise chloroquine,
hydroxychloroquine and amodiaquine plus optional non-active ingredients. As
above, the non-active ingredients may comprise ethyl alcohol and peppermint
spirit oil, and the gel form may additionally comprise lidocaine jelly or
ointment,
while the spray form may additionally comprise lidocaine as a 2% solution. A
particularly preferred composition is set forth below:
Chloroquine phosphate 4000 mg (8 500-mg tablets)
Hydroxychloroquine sulphate 2400 mg (12 200-mg tablets)
Amodiaquine hydrochloride 800 mg (4 200-mg tablets)
Lidocaine jelly 2% 10 ml
Ethyl alcohol (70% aqueous solution) 15 ml
Peppermint spirit oil 2.5 ml
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Water 2.5 ml
Preferably, this composition is prepared by crushing the chloroquine
phosphate tablets together with both the hydroxychloroquine sulphate tablets
and the amodiaquine hydrochloride tablets in a mortar, and then adding each of
the non-active ingredients, in the sequence listed above, sufficient to make a
total of about 30 gm of the gel or spray. The gel form may then be transferred
to a tube or other appropriate container, while the spray form may then be
transferred into a conventional spray bottle.
The gel forn, of this medication is preferably administered to a patient as
follows. The affected areas are first cleaned with one or more alcohol swabs,
and optionally, each wart to be treated may then be filed for approximately 30
seconds with a conventional nail filing device or instrument (which can be
purchased from a variety of sources, including beauty supply shops); only
warts
that appear on the toes, fingers, elbows, knees and other hard surfaces of the
patient's skin should be filed, whereas warts appearing on soft tissues, such
as
the genitalia or in the oral cavity, need not (and should not) be filed. This
filing,
although optional, is preferred since such filing accelerates removal of the
wart(s) Thereafter, an amount of the gel approximately equal to the surface
area
of each wart (or an amount equal to the surface area of the tip of a finger)
is
applied to the affected area, after which that area may optionally be covered
with
a sterile bandage. The gel form is preferably administered to the patient in
the
foregoing manner once or twice a day, for approximately one to four weeks,
until
disappearance of the wart(s). The spray form of this medication is preferably
administered to a patient in the same manner, although the dosage is
preferably
two puffs applied to the affected areas once or twice daily.
When the compositions of the invention comprising chloroquine in
combination with both hydroxychloroquine and amodiaquine as the active
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ingredients are to be administered transdermally, in the form of a patch,
approximately 3.5 am of the gel form (prepared as described above) may be
transferred to the pad of a conventional 3.5 mini-patch. This form of the
medication is preferably administered to a patient in the same manner as the
gel
form, although the dosage for the patch form preferably constitutes applying a
patch to each affected area once a day, and replacing it with a fresh patch
once
every 24 hours (approximately), until disappearance of the wart(s). It is to
be
understood that the patch form can also be used to cover the scars left after
conventional surgical removal of a wart, with replacement every other day, in
order to prevent re-growth of the wart.
In-vivo experimental results which demonstrate the efficacy of the
foregoing compositions are set forth below. Specifically, the following
working
examples illustrate both the manner in which a representative sample of the
compositions of the present invention have been used in human subjects
suffering from at least one wart associated with infections of the human
papillomavirus, and the experimental results obtained, which demonstrate the
efficacy of the invention.
Example 1
A juvenile male, specifically a 12-year old boy of Hispanic ancestry. was
observed as having warts on three out of five fingers of the right hand. These
warts were first filed in the manner set forth above for better contact with
the
medication, and they were then treated with a composition in gel form
containing
hydroxychloroquine as the only active ingredient (prepared in the manner set
forth above for such compositions). This gel composition was applied to each
of the warts, in an amount approximately equal to the surface area of each
wart,
once or twice a day for approximately one week, following which it was
observed
that all of the warts had disappeared completely, without leaving any visible
scarring.
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Example 2
Another juvenile male, specifically a 15-year old boy also of Hispanic
ancestry, presented with warts on his fingers. The same composition as in
Example 1 was applied, in the same manner and with the same frequency as in
Example 1, and after approximately one week of such treatments, similar
results
were observed; that is, all of the warts had disappeared completely, without
leaving any visible scarring.
Example 3
An adult male, specifically a 55-year old man of Hispanic ancestry. was
observed to have genital warts, specifically, warts scattered about the skin
of the
scrotum. The same composition as in Example 1 was applied, in the same
manner and with the same frequency as in Example 1, and after approximately
one week of such treatments it was observed that 50% of the mass of the warts
had disappeared. Thereafter, the patient switched to treatments with a
composition in gel form containing chloroquine as the only active ingredient
(prepared in the manner set forth above for such compositions), and after two
days of similar twice-daily treatments with the latter composition, it was
observed
that the remaining 50% of the mass of the warts had disappeared.
ExampleA
An adult female, specifically a 50-year old black woman, and her male
partner, a 24-year old man of mixed Hispanic and black ancestry, both of whom
presented with genital warts. The female, who was also living with a human
immunodeficiency virus (HIV) infection, reported warts on her labia majora,
which were then treated with a composition in gel form containing chloroquine
as the only active ingredient (prepared in the manner set forth above for such
compositions). This gel composition was applied to each of the warts, in an
amount approximately equal to the surface area of each wart, once or twice a
day for approximately four weeks, after which the patient reported that she
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observed a great deal of improvement. Thereafter, the female patient switched
to treatments with a composition in gel form containing chloroquine and
amodiaquine as the active ingredients (prepared in the manner set forth above
for such compositions), and after approximately two weeks of similar twice-
daily
treatments with the latter composition, she reported that the warts had
disappeared.
The same treatment regime was used on her male partner, who
presented with warts on his penis, and who, in addition, reported having been
born with HIV. After three months it was observed that the warts had
disappeared completely. It is believed that this patient may have required a
longer duration of treatment to achieve a successful result due to his
underlying
HIV infection, which possibly may have reduced the ability of his immune
system
to combat the human papillomavirus infection.
Example 5
Another adult male, specifically a 36-year old man of Hispanic ancestry,
was observed as having warts on one of his fingers. The same composition as
in Example 1 was applied, in the same manner and with the same frequency as
in Example 1 and after two days of such treatments, similar results were
observed: that is, all of the warts had disappeared completely, without any
visible
scarring.
Example 6
Another adult female, specifically a 45-year old woman of Hispanic
ancestry, presented with warts on her fingers. These warts were treated with a
composition in gel form containing chloroquine as the only active ingredient
(prepared in the manner set forth above for such compositions), which was
applied in the same manner as in Example 1. After three days of such
treatments, the patient reported that all of the warts had disappeared
completely,
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without any visible scarring.
Example 7
Another juvenile male, specifically a 16-year old boy also of Hispanic
ancestry, presented with two warts on his hand. After filing, a composition in
gel
form containing amodiaquine as the only active ingredient (prepared in the
manner set forth above for such compositions) was applied to each wart, in the
same manner and with the same frequency as in Example 1, and after
approximately one week of such treatments, the warts were reduced in size by
approximately 50%. Following a second week of similar treatments, both of the
warts had disappeared completely.
Example 8
Two juvenile females, specifically a 16-year old girl and her 14-year old
sister, both also of Hispanic ancestry, each presented with warts on their
feet -
the 16-year old had two large warts on one foot, which made walking difficult
for
her without pain, while the 14-year old had one smaller wart on one of her
feet.
After filing, a composition in gel form containing the combination of
chloroquine
and hydroxychloroquine as the active ingredients (prepared in the manner set
forth above for such compositions) was applied generously to all of the warts
on
the feet of both patients. After approximately three weeks of such treatments
twice a day, all of the warts had disappeared completely from the feet of both
patients.
Example 9
An adult male, specifically a 50-year old West African man from Senegal,
presented with many different warts on his feet. After filing, a composition
in gel
form containing the combination of chloroquine. hydroxychioroquine and
amodiaquine as the active ingredients (prepared in the mariner set forth above
for such compositions) was applied to the warts, as well as to the areas of
his
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feet that were unaffected. After two weeks of such treatments twice a day, all
of the warts had disappeared completely from both of his feet, allowing the
patient to walk and wear shoes comfortably.
Example 10
An adult male, specifically a 50-year old West African man from Nigeria,
was observed to have two (2) genital warts on the shaft of his penis. These
warts were treated with a composition in gel form containing chloroquine as
the
only active ingredient (prepared in the manner set forth above for such
compositions). This gel composition was applied to each of the warts, in an
amount approximately equal to the surface area of each wart, once a day for
two
weeks, following which it was observed that both warts had disappeared
completely, leaving the skin flat. This patient was observed as never having a
recurrence of the warts.
Example 11
An adult male, specifically a 40-year old West African man from Nigeria,
was observed to have a genital wart on the shaft of his penis. This wart was
treated with a composition in gel form containing chloroqine and amodiaquine
as the active ingredients (prepared in the manner set forth above for such
compositions). This gel composition was applied to the wart, in an amount
approximately equal to the surface area of the wart, and the area was then
covered with an adhesive bandage, once a day for two weeks, following which
it was observed that the wart had disappeared completely, leaving the skin
fiat.
This patient was observed as never having a recurrence of the warts.
Example 12
A juvenile female, specifically a 15-year old girl of Nigerian ancestry, was
observed as having two plantar warts (located on the bottom of her right
foot).
These warts were treated with a composition in gel form containing chloroqine
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and hydroxychloroquine as the active ingredients (prepared in the manner set
forth above for such compositions). This gel composition was applied to each
of the warts, in an amount approximately equal to the surface area of each
wart,
and the area was then covered with an adhesive bandage, once a day for three
weeks, following which it was observed that both warts had disappeared
completely, leaving the skin flat. This patient was observed as never having a
recurrence of the warts.
Apart from the foregoing examples, in vitro experimental data have been
obtained which strongly indicate that the compositions of the present
invention
are highly active in inhibiting replication of the human papillomavirus. Tests
were
conducted to assess the activity of each of chloroquine, hydrogchloroquine and
amodiaquine, as compared with the activity of cidofovir, a known inhibitor of
replication of the human papillomavirus ('HPV").
Specifically, in these tests, vectors for expression of an HPV genotype-
matched set of viral El and E2 proteins (derived from virus strain HPV-11)
along
with an HPV ori-containing plasmid were cotransfected into HEK293 cells, The
cells were cultured in the absence or presence of the test compounds
(chloroquine, hydroxychloroquine, and amodiaquine), each atl 10, and 100 pM
concentrations Low molecular weight DNA was harvested 2 days post-
and digested with Dpn 1 and exonuclease Ill to remove unreplicated
transfected plasmid DNA. The replicated DNA was then subjected to real time
qPCR (quantitative poiymerase chain reaction) analyses in triplicate. Two
controls were performed. One was to omit the El expression vector to provide
a background amount of undigested and unreplicated DNA. The other, positive
control was treatment with the known inhibitor cidofovir, as mentioned above.
A toxicity assay based upon cell viability at the time of harvest on day 2 was
performed alongside each transient replication assay in 293 cells. The test
compounds were added 4 hours post transfection for a total exposure of 44
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hours. More than 1 x 10 cells were scored in a BioRad Automatic Cell Counter,
with a determination of the total numbers, the numbers of trypan blue stained
(dead) cells, and the % of dead cells.
The results of these tests are set forth below in Table 1, in which EC50
represents the concentration of the tested compound that reduces viral
replication by 50%. EC50 represents the concentration of the tested compound
that reduces viral replication by 90%, CC5, represents the concentration of
the
tested compound that reduces cell viability by 50%, SIõ represents CC60/EC,0,
and SI,,o represents CC/ECõ.
Table 1
Compound ECsa ECõ CC 60 Slso
Cidofovir 148.00 >200.00 >200.00
>1 1
Chloroquine 3.00 28.00 >100.00 >33 >4
Hydroxychloroquine >100.00 >100.00 >100.00 1 1
Amodiaquine 5.00 58.00 >100.00 >20 >2
Based on the experimental examples and test results summarized above,
it is believed that the present invention comprises treatment methods and
compositions that can treat infections caused by the human papillomavirus and
can remove warts associated with that virus and prevent the recurrence of such
warts, all by inhibiting replication of the virus. It is also believed that
the removal
of such warts, particularly the rectal and genital warts and those found in
the oral
cavity associated with the sexually transmitted types of the human
papillomavirus, will reduce the risk of spreading that virus, and will
therefore
subsequently reduce the morbidity and mortality rates associated with
cervical,
vaginal, vulvar. penile, anal, rectal and/or oropharyngeal cancers. It is
further
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believed that the methods and compositions of the present invention can be
used as a prophylactic treatment, to provide protection during sexual
intercourse
from infections of the human papillomavirus for individuals who have not yet
been infected.
It is also believed that the compositions and methods of the present
invention may also be effective to treat infections in other mammalian
species,
caused by non-human papillomaviruses that may be specific to such species,
and may be effective to remove warts associated with those viruses and to
prevent the recurrence of such warts, all by inhibiting the replication of
such non-
human papillomaviruses in the same manner as with the human papillomavirus.
This belief is based upon the close similarities among the various mammalian
papillomaviruses, in terms of the organization of the viral genome, and in
terms
of the behavior of the viral proteins and the manner in which those proteins
interact with host proteins. All papillomaviruses, regardless of type or the
species they infect, need to modulate the host's immune system, which is
accomplished with three viral proteins, designated E5, E6 and E7, which
slightly
modify the host's cells, making it difficult for the host's immune system to
fight
back.
Thus, since the target tissues, infection cycles and reproductive programs
of all papillomaviruses are quite similar, independent of the papillomavirus
type
or the species infected, it is reasonable to conclude not only that all such
viruses
are dependent upon the same host properties and functions, but also that all
such viruses would be susceptible to similar host inhibitors as well as
pharmacological inhibitors, such as those which are disclosed herein.
Accordingly, the applicant strongly believes that the compositions and methods
of the present invention will be effective to treat infections of non-human
papillomaviruses in other mammalian species, and to inhibit the replication of
papillomaviruses in such species.
CA 02927146 2015-12-23
WO 2014/008248
PCT/US2013/049046
-34-
While there has been described what are at present considered to be the
preferred embodiments of the present invention, it will be apparent to those
skilled in the art that the embodiments described herein are by way of
illustration
and not of limitation. Various modifications of the disclosed embodiments. as
well as alternative embodiments of the invention, will become apparent to
persons skilled in the art upon reference to the description of the invention.
Therefore, it is to be understood that various changes and modifications may
be
made in the embodiments disclosed herein without departing from the true
spirit
and scope of the present invention.
