NZ738063B2 - Stable povidone-iodine compositions - Google Patents
Stable povidone-iodine compositions Download PDFInfo
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- NZ738063B2 NZ738063B2 NZ738063A NZ73806312A NZ738063B2 NZ 738063 B2 NZ738063 B2 NZ 738063B2 NZ 738063 A NZ738063 A NZ 738063A NZ 73806312 A NZ73806312 A NZ 73806312A NZ 738063 B2 NZ738063 B2 NZ 738063B2
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- pvp
- composition
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- steroid
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- 239000000203 mixture Substances 0.000 title claims abstract description 261
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Abstract
Disclosed herein are povidone-iodine (PVP-I) containing compositions, as well as methods of making such compositions, which provide reliable stability for PVP-I preparations, including preparations comprising PVP-I and one or more additional components. The compositions may optionally comprise a non-steroidal anti-inflammatory agent such as amfenac, ketorlac or a steroid such as dexamethasone. The compositions are suitable for topical application and can be used in treating an eye disorder or microorganism infection of at least one tissue of the eye. -steroidal anti-inflammatory agent such as amfenac, ketorlac or a steroid such as dexamethasone. The compositions are suitable for topical application and can be used in treating an eye disorder or microorganism infection of at least one tissue of the eye.
Description
TITLE
Stable Povidone-Iodine Compositions
This application is a divisional of New Zealand patent application 720420, which
is itself a divisional of New Zealand patent application 623082, which is the national
phase entry in New Zealand of PCT international application
(published as ).
BACKGROUND
Povidone-iodine (“PVP-I”) has various uses, including treatment of burns and of
different skin lesions (e.g., decubitus and leg ulcers). In some preparations, it is available
for the therapy of inflammations in the ear, mouth and pharynx, and for vaginitis. PVP-I is
used in the treatment of skin disinfection in the prevention of nosocomial infections,
especially, prior to invasive procedures such as the insertion of peripheral catheters,
treatment of exit site infection.
PVP-I is effective against variety of microorganisms, including bacteria, viruses,
and fungi. The use of PVP-I can circumvent problems found with more traditional
antibiotics, such as antibiotic resistance and problems with compound versatility. For
example, otitis media (middle ear infection) occurs in the area between the ear drum and
the inner ear, including the Eustachian tube. Ear infection (particularly in children) is one
of the many diseases that have become hard to treat with traditional antibiotic drugs
because of antibiotic resistant bacteria and antibiotic-resistant microorganisms. Most cases
of otitis media, for example, are caused by one of several major pathogens, Streptococcus
pneumonia, Haemophilus influenza, Moraxella catarrhalia, Staphylococcus aureus,
Staphylococcus epidermidis, or Pseudomonas aeruginosa. PVP-I is effective against these
organisms, and in one example, would be useful for treatment of otitis media in cases in
which the tympanic membrane is breeched or damaged, to allow penetration of the PVP-I
solution.
However, PVP-I solutions sometimes lack predictable stability. Furthermore, the
combination of PVP-I with other components is well-documented to render the PVP-I
unpredictably unstable. For example, PVP-I is useful for treatment of ophthalmic
conditions. In U.S. Patent 7,767,217, it is shown that under certain specific conditions,
dexamethasone can be combined with PVP-I to form an effective antimicrobial-steroid
pharmaceutical composition. However, it is also shown that most preparations which
combine PVP-I (or iodine) with a steroid suffer from instability due, in part, to reactivity
of the iodine with the steroid. In fact, U.S. Patent 3,886,268 demonstrates the well-known
instability of steroid-iodine combinations.
It is an object of the present invention to go at least some way to overcoming any
one or more of these disadvantages and/or to at least provide the public with a useful
choice.
In this specification where reference has been made to patent specifications, other
external documents, or other sources of information, this is generally for the purpose of
providing a context for discussing the features of the invention. Unless specifically stated
otherwise, reference to such external documents is not to be construed as an admission that
such documents, or such sources of information, in any jurisdiction, are prior art, or form
part of the common general knowledge in the art.
SUMMARY
In a first aspect, the present invention provides a composition suitable for topical
administration, comprising a mixture of a) povidone-iodine (PVP-I) at a starting
concentration between about 0.001% and about 12.5% by weight; and b) at least one non-
steroidal anti-inflammatory (NSAID), which is amfenac or a salt thereof.
In a further aspect, the present invention provides use of PVP-I and at least one
non-steroidal anti-inflammatory (NSAID), which is amfenac or a salt thereof, for the
manufacture of a medicament for treating an eye disorder or a microorganism infection of
at least one tissue of the eye, wherein the starting concentration of the PVP-I is between
about 0.001% and about 12.5% by weight.
Described herein is a composition that is suitable for topical administration,
comprising povidone-iodine (PVP-I) at a starting concentration between about 0.4% and
about 12.5% by weight, wherein after a period of one month after preparing the
composition, the PVP-I concentration is at least 98% of the PVP-I starting concentration,
and after a period of six months after preparing the composition, the PVP-I concentration
is at least 96% of the PVP-I starting concentration.
Described herein is a composition that is suitable for topical administration,
comprising a mixture of PVP-I at a starting concentration between about 0.4% and about
12.5% by weight and at least one non-steroidal anti-inflammatory (NSAID) selected from
the group consisting of amfenac, bromfenac, ketotifen fumarate, diclofenac, diclofenac
sodium, flurbiprofen sodium, ketorlac, ketorlac tromethamine, suprofen, celecoxib,
naproxen, rofecoxib, and combinations and salts thereof, wherein after a period of one
month after mixing the NSAID and PVP-I to form the composition, the PVP-I
concentration is at least 98% of the PVP-I starting concentration, and after a period of six
months after mixing the NSAID and PVP-I to form the composition, the PVP-I
concentration is at least 96% of the PVP-I starting concentration.
Described herein is a composition that is suitable for topical administration,
comprising a mixture of PVP-I at a starting concentration between about 0.4% and about
12.5% by weight and at least one steroid selected from the group consisting of
dexamethasone, dexamethasone alcohol, dexamethasone sodium phosphate,
fluorometholone acetate, fluorometholone alcohol, loteprednol etabonate, medrysone,
prednisolone acetate, prednisolone sodium phosphate, difluprednate, rimexolone,
hydrocortisone, hydrocortisone acetate, lodoxamide tromethamine, and combinations and
salts thereof, wherein after a period of one month after mixing the steroid and PVP-I to
form the composition, the PVP-I concentration is at least 98% of the PVP-I starting
concentration, and after a period of six months after mixing the steroid and PVP-I to form
the composition, the PVP-I concentration is at least 96% of the PVP-I starting
concentration.
Described herein is a composition that is suitable for topical administration,
comprising a mixture of PVP-I at a starting concentration between about 0.4% and about
12.5% by weight, and at least one steroid selected from the group consisting of
dexamethasone, dexamethasone alcohol, dexamethasone sodium phosphate,
fluorometholone acetate, fluorometholone alcohol, loteprednol etabonate, medrysone,
prednisolone acetate, prednisolone sodium phosphate, difluprednate, rimexolone,
hydrocortisone, hydrocortisone acetate, lodoxamide tromethamine, and combinations and
salts thereof, wherein after a period of one month after mixing the steroid and PVP-I to
form the composition, the PVP-I concentration is at least 98% of the PVP-I starting
concentration, and after a period of six months after mixing the steroid and PVP-I to form
the composition, the PVP-I concentration is at least 96% of the PVP-I starting
concentration, further wherein, after a period of one month after mixing the steroid and
PVP-I to form the composition, the steroid concentration is at least 90% of the steroid
starting concentration.
Described herein is a method for treating a mammal having an otic infection, the
method comprising contacting the ear of the mammal with a composition disclosed herein.
In an embodiment, a composition is provided that is suitable for topical
administration, comprising PVP-I at a starting concentration between about 0.001% and
about 0.6% by weight, wherein after a period of one month after preparing the
composition, the PVP-I concentration is at least 93% of the PVP-I starting concentration,
and after a period of six months after preparing the composition, the PVP-I concentration
is at least 93% of the PVP-I starting concentration.
Described herein is a composition that is suitable for topical administration,
comprising a mixture of PVP-I at a starting concentration between about 0.001% and
about 0.6% by weight, and at least one NSAID selected from the group consisting of
amfenac, bromfenac, ketotifen fumarate, diclofenac, diclofenac sodium, flurbiprofen
sodium, ketorlac, ketorlac tromethamine, suprofen, celecoxib, naproxen, rofecoxib, and
combinations and salts thereof, wherein after a period of one month after mixing the
NSAID and PVP-I to form the composition, the PVP-I concentration is at least 93% of the
PVP-I starting concentration, and after a period of six months after mixing the NSAID and
PVP-I to form the composition, the PVP-I concentration is at least 93% of the PVP-I
starting concentration.
Described herein is a composition that is suitable for topical administration,
comprising a mixture of PVP-I at a starting concentration between about 0.001% and
about 0.6% by weight, and at least one steroid selected from the group consisting of
dexamethasone, dexamethasone alcohol, dexamethasone sodium phosphate,
fluorometholone acetate, fluorometholone alcohol, loteprednol etabonate, medrysone,
prednisolone acetate, prednisolone sodium phosphate, difluprednate, rimexolone,
hydrocortisone, hydrocortisone acetate, lodoxamide tromethamine, and combinations and
salts thereof, wherein after a period of one month after mixing the steroid and PVP-I to
form the composition, the PVP-I concentration is at least 93% of the PVP-I starting
concentration, and after a period of six months after mixing the steroid and PVP-I to form
the composition, the PVP-I concentration is at least 93% of the PVP-I starting
concentration.
Described herein is a composition that is suitable for topical administration,
comprising a mixture of PVP-I at a starting concentration between about 0.001% and
about 0.6% by weight, and at least one steroid selected from the group consisting of
dexamethasone, dexamethasone alcohol, dexamethasone sodium phosphate,
fluorometholone acetate, fluorometholone alcohol, loteprednol etabonate, medrysone,
prednisolone acetate, prednisolone sodium phosphate, difluprednate, rimexolone,
hydrocortisone, hydrocortisone acetate, lodoxamide tromethamine, and combinations and
salts thereof, wherein after a period of one month after mixing the steroid and PVP-I to
form the composition, the PVP-I concentration is at least 93% of the PVP-I starting
concentration, and after a period of six months after mixing the steroid and PVP-I to form
the composition, the PVP-I concentration is at least 93% of the PVP-I starting
concentration, further wherein, after a period of one month after mixing the steroid and
PVP-I to form the composition, the steroid concentration is at least 90% of the steroid
starting concentration.
Described herein is a method for treating an eye disorder or a microorganism
infection of at least one tissue of the eye comprising the step of administering one or more
doses of a composition disclosed herein to the eye.
Described herein is an ophthalmic composition that is suitable for topical
administration to an eye, effective for treatment and/or prophylaxis of a microorganism
infection or a disorder of at least one tissue of the eye, comprising a mixture of PVP-I at a
starting concentration between about 0.4% and about 1.0% by weight, and at least one
steroid selected from the group consisting of dexamethasone, dexamethasone alcohol,
dexamethasone sodium phosphate, fluorometholone acetate, fluorometholone alcohol,
loteprednol etabonate, medrysone, prednisolone acetate, prednisolone sodium phosphate,
difluprednate, rimexolone, hydrocortisone, hydrocortisone acetate, lodoxamide
tromethamine, and combinations and salts thereof, wherein after a period of one month
after mixing the steroid and PVP-I to form the composition, the PVP-I concentration is at
least 98% of the PVP-I starting concentration, and after a period of six months after
mixing the steroid and PVP-I to form the composition, the PVP-I concentration is at least
96% of the PVP-I starting concentration.
Described herein is an ophthalmic composition that is suitable for topical
administration to an eye, effective for treatment and/or prophylaxis of a microorganism
infection or a disorder of at least one tissue of the eye, comprising a mixture of PVP-I at a
starting concentration between about 0.1% and about 0.6% by weight, and at least one
steroid selected from the group consisting of dexamethasone, dexamethasone alcohol,
dexamethasone sodium phosphate, fluorometholone acetate, fluorometholone alcohol,
loteprednol etabonate, medrysone, prednisolone acetate, prednisolone sodium phosphate,
difluprednate, rimexolone, hydrocortisone, hydrocortisone acetate, lodoxamide
tromethamine, and combinations and salts thereof, wherein after a period of one month
after mixing the steroid and PVP-I to form the composition, the PVP-I concentration is at
least 93% of the PVP-I starting concentration, and after a period of six months after
mixing the steroid and PVP-I to form the composition, the PVP-I concentration is at least
93% of the PVP-I starting concentration.
In an embodiment, a composition is provided that is suitable for topical
administration, comprising PVP-I at a starting concentration between about 0.4% and
about 12.5% by weight, wherein after a period of one month after preparation of the
composition, the PVP-I concentration is within about 2% to about 3% of the PVP-I
starting concentration, and after a period of six months after preparation of the
composition, the PVP-I concentration is within about 2% to about 3% of the PVP-I
concentration at one month after preparation of the composition.
In an embodiment, a composition is provided that is suitable for topical
administration, comprising PVP-I at a starting concentration between about 0.001% and
about 0.6% by weight, wherein after a period of one month after preparation of the
composition, the PVP-I concentration is about 5% to about 10% below the PVP-I starting
concentration, and after a period of six months after preparation of the composition, the
PVP-I concentration is within about 1% of the PVP-I concentration at one month after
preparation of the composition.
In the description in this specification reference may be made to subject matter
which is not within the scope of the appended claims. That subject matter should be
readily identifiable by a person skilled in the art and may assist in putting into practice the
invention as defined in the appended claims.
DETAILED DESCRIPTION
It is known that iodine, including preparations of PVP-I, can react chemically with
various substances, making iodine in solution unstable. As shown in U.S. Patent No.
,126,127, incorporated herein by reference in its entirety, PVP-I solutions have been
packaged for medicinal use, e.g. in soft plastic bottles or containers, which can be used for
various medicinal purposes. However, one problem that has been encountered with such
packaged iodophor solutions is that elemental iodine (equilibrium iodine) has leached
through the packaging itself. In the past, this resulted both in a decrease in stability and
medicinal capacity of the iodophor solution contained within the packaging, and made it
difficult to handle such packaging since the elemental iodine which leached through
caused staining, and in some cases, leakage. The problems associated with packaging
such PVP-I solutions in soft plastic bottles or containers have been overcome through the
addition of other stabilizers or iodine donating species such as iodate salts, as disclosed in
U.S. Pat. No. 4,113,857, and the use of iodide salts, as disclosed in U.S. Pat. No.
4,996,048. However, the addition of unwanted components is undesirable, and sometimes
creates undesirable side effects and increases product cost.
Although PVP-I solutions are known to exert microbicidal activity, stabilizing
PVP-I solutions for various uses (e.g., ophthalmic use) can be problematic. Furthermore,
in view of the stability problems associated with dilute PVP-I solutions, it is difficult to
provide an acceptable formulation for dilute PVP-I solutions, such as for ophthalmic use.
For example, the introduction of donating species such as iodate into a PVP-I solution is
not considered to be desirable when the solution is to be used as an ophthalmic preparation
because iodate and iodide are known to be irritating and toxic to the pigment epithelium of
the retina. Thus, a PVP-I solution stabilized via the addition of, for example, potassium
iodide and/or potassium iodate would not be useful as an ophthalmic preparation.
Furthermore, compositions comprising PVP-I and a steroid may suffer from
instability due to the reactivity between iodine and the steroid. The affinity of free iodine
for reaction with --OH, --SH and --NH functional groups is well described in the literature
and forms the basis for the anti-microbial activity of iodine-containing solutions (Rackur
H. J. Hosp. Infect., 1985; 6: 13-23, and references therein). Dexamethasone, (9-Fluoro-
11.beta., 17, 21-trihydroxy-16.alpha.-methylpregna-1, 4-diene-3, 20-dione) for example,
contains three such moieties (--OH) at the 11, 17 and 21 positions. The skilled artisan
would conclude that these hydroxyl groups would be prone to covalent substitution
reactions by the free iodine generated in the solution equilibrium reaction described above
for PVP-I. .
The compositions and methods disclosed herein provide reliable stability for PVP-I
preparations, including preparations comprising PVP-I and one or more additional
components. The characteristics of the stability of a PVP-I composition encompassed
herein are referred to herein as a “stability profile”.
In an aspect, the PVP-I compositions disclosed herein demonstrate stability
through a multi-phasic degradation mechanism. In another aspect, the PVP-I
compositions disclosed herein demonstrate stability through a multi-phasic degradation
mechanism, with reference to the time at which the composition is prepared. In an
embodiment, a PVP-I composition demonstrates stability by way of a biphasic degradation
pattern. In an embodiment, PVP-I degrades at a first rate in the first phase, followed by a
second phase in which PVP-I degrades more slowly in comparison to the rate of
degradation during the first phase.
“Stability”, as the term is used herein, refers to the degradation of PVP-I. In
particular, degradation of PVP-I includes, among other things, the loss of iodine from
PVP-I.
“Compatibility”, as the term is used herein, refers to the ability of a substance to
co-exist in a composition with PVP-I, without being oxidized by PVP-I.
The term “comprising” as used in this specification and claims means “consisting
at least in part of”. When interpreting statements in this specification and claims which
include the term “comprising”, other features besides the features prefaced by this term in
each statement can also be present. Related terms such as “comprise” and “comprises” are
to be interpreted in similar manner.
In an aspect, a PVP-I composition demonstrates stability by way of a unique
biphasic degradation pattern depending upon the starting concentration of the PVP-I
composition. In an embodiment, the rate of degradation of PVP-I in the first phase, the
rate of PVP-I degradation in the second phase, and the relative rate of degradation of PVP-
I in the first and second phases all may differ, either independently or dependent upon one
another, based upon the starting concentration. In an embodiment, the stability profile of a
PVP-I composition may be affected by the addition to or the removal of any additional
components from the composition. In another embodiment, the stability profile of a PVP-I
composition may be affected by the concentration of any additional components in the
composition. In an embodiment, the stability profile of a PVP-I composition may be
affected by one or more of stirring, agitation, application of heat, cooling of the
composition, or by the adjustment of any physical or chemical parameter of the
composition.
Compositions
In an embodiment, disclosed herein is composition comprising PVP-I at a starting
concentration between about 0.4% and about 12.5% by weight, wherein after a period of
one month after preparing the composition, the PVP-I concentration is at least 98% of the
PVP-I starting concentration, and after a period of six months after preparing the
composition, the PVP-I concentration is at least 96% of the PVP-I starting concentration.
In another embodiment, disclosed herein is a composition comprising PVP-I at a starting
concentration between about 0.001% and about 0.6% by weight, wherein after a period of
one month after preparing the composition, the PVP-I concentration is at least 93% of the
PVP-I starting concentration, and after a period of six months after preparing the
composition, the PVP-I concentration is at least 93% of the PVP-I starting concentration.
In an embodiment, the composition further comprises an NSAID.
In another embodiment, the composition further comprises a steroid. In an
embodiment, after a period of one month after mixing the steroid and PVP-I to form the
composition, the steroid concentration is at least 90% of the steroid starting concentration.
The compositions disclosed herein are useful for topical administration, including,
but not limited to, application to the eye, the skin, the ear, nasal passages, sinuses, and the
vagina.
In an embodiment, a composition comprises PVP-I at a concentration in the range
of about 0.001% to about 0.75%. In another embodiment, a composition comprises PVP-I
at a concentration in the range between 0.005% and 0.7%. In another embodiment, a
composition comprises PVP-I at a concentration in the range between 0.01% and 0.65%.
In another embodiment, a composition comprises PVP-I at a concentration in the range
between 0.05% and 0.6%. In another embodiment, a composition comprises PVP-I at a
concentration in the range between 0.1% and 0.5%. In another embodiment, a
composition comprises PVP-I at a concentration in the range between 0.1% and 0.4%, and
in yet another embodiment, between 0.1% and 0.3%. In an embodiment, a composition
comprises PVP-I at a concentration in the range of about 0.1% to about 0.25%, about 0.1%
to about 0.2%, and about 0.1% to about 0.15%.
In an embodiment, a composition comprises PVP-I at a concentration in the range
of about 0.3% to about 12.5%. In another embodiment, a composition comprises PVP-I at
a concentration in the range between 0.4% and 12.5%. In another embodiment, a
composition comprises PVP-I at a concentration in the range between 0.5% and 12.5%. In
another embodiment, a composition comprises PVP-I at a concentration in the range
between 0.6% and 12.5%. In another embodiment, a composition comprises PVP-I at a
concentration in the range between 0.7% and 12.5%. In another embodiment, a
composition comprises PVP-I at a concentration in the range between 0.8% and 12.5%,
and in yet another embodiment, between 0.9% and 12.5%. In an embodiment, a
composition comprises PVP-I at a concentration in the range of about 1.0% to about
12.5%, about 2.0% to about 12.5%, about 3.0% to about 12.5%, about 4.0% to about
12.5%, about 5.0% to about 12.5%, about 7.5% to about 12.5%, and about 10.0% to about
12.5%.
In an embodiment, a composition comprises PVP-I at a concentration in the range
of about 0.001% to about 12.5%. In another embodiment, a composition comprises PVP-I
at a concentration in the range between 0.01% and 10.0%. In another embodiment, a
composition comprises PVP-I at a concentration in the range between 0.05% and 7.5%. In
another embodiment, a composition comprises PVP-I at a concentration in the range
between 0.1% and 5.0%. In another embodiment, a composition comprises PVP-I at a
concentration in the range between 0.1% and 2.5%. In another embodiment, a
composition comprises PVP-I at a concentration in the range between 0.2% and 1.5%, and
in yet another embodiment, between 0.3% and 1.0%. In an embodiment, a composition
comprises PVP-I at a concentration in the range of about 0.2% to about 2.0%, about 0.3%
to about 1.5%, about 0.36% to about 1.0%, and about 0.4% to about 0.75%.
In an embodiment, a composition comprises PVP-I at a concentration of about
0.001%, about 0.005%, about 0.01%, about 0.05%, about 0.1%, about 0.2%, about 0.3%,
about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%,
about 2.5%, about 5%, about 7.5%, about 10%, or about 12.5%. In an embodiment, a
composition comprises povidone-iodine PVP-I at a concentration of 0.001%, 0.005%,
0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 2.5%, 5%,
7.5%, 10.0%, or 12.5%. In another embodiment, a composition comprises PVP-I at a
concentration of about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about
7%, about 8%, about 9%, about 10%. In another embodiment, a composition comprises
PVP-I at a concentration of about 2% or less, about 3% or less, about 4% or less, about 5%
or less, about 6% or less, about 7% or less, about 8% or less, about 9% or less or about
% or less. In another embodiment, a composition comprises PVP-I at a concentration of
about 0.1% or more, about 0.2% or more, about 0.3% or more, about 0.4% or more, about
0.5% or more, about 0.6% or more, about 0.7% or more, about 0.8% or more, about 0.9%
or more, 1% or more, about 2% or more, about 3% or more, about 4% or more, about 5%
or more, about 6% or more, about 7% or more, about 8% or more, about 9% or more or
about 10% or more. In another embodiment, a composition comprises PVP-I at a
concentration of 0.001%, 0.005%, 0.01%, 0.05%, 0.1%. 0.2%, 0.3%, 0.4%, 0.5%, 0.6%,
0.7%, 0.8%, 0.9%, 1.0%, 2.0%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0% or 10.0%.
Compositions disclosed herein may further comprise one or more additional
components.
In an embodiment, compositions disclosed herein comprise PVP-I and a steroid.
In another embodiment, a composition disclosed herein is a pharmaceutical composition.
In another embodiment, a composition disclosed herein is an ophthalmic composition.
In an embodiment, compositions disclosed herein may further comprise one or
more steroids. Steroids include, but are not limited to, dexamethasone, dexamethasone
alcohol, dexamethasone sodium phosphate, fluorometholone acetate, fluorometholone
alcohol, loteprednol etabonate, medrysone, prednisolone acetate, prednisolone sodium
phosphate, difluprednate, rimexolone, hydrocortisone, hydrocortisone acetate, lodoxamide
tromethamine, and any combinations thereof. The steroid may be used any form, and in
various modified forms such as acetate forms, and sodium phosphate forms, sodium salts,
and the like. In an embodiment, a pharmaceutically acceptable salt of the steroid is used.
In an embodiment, compositions disclosed herein may further comprise one or
more non-steroidal anti-inflammatory compounds (NSAIDS). NSAIDS include, but are
not limited to, amfenac, bromfenac, ketotifen fumarate, diclofenac, diclofenac sodium,
flurbiprofen sodium, ketorlac, ketorlac tromethamine, suprofen, celecoxib, naproxen,
rofecoxib, or a derivative or combination thereof. Pharmaceutically-acceptable salts of
NSAIDS are also contemplated herein.
In an embodiment, a steroid and/or NSAID is present in the composition at a level
of about 0.001% to about 10%. In an embodiment, a steroid and/or NSAID is present in
the composition or preparation at a level of 0.001%, 0.002%, 0.003%, 0.004%, 0.005%,
0.006%, 0.007%, 0.008%, 0.009%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%,
0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%,
1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, or 2.0%. In an
embodiment, a steroid and/or NSAID is present in the composition or preparation at a
level of about 0.001%, about 0.002%, about 0.003%, about 0.004%, about 0.005%, about
0.006%, about 0.007%, about 0.008%, about 0.009%, about 0.01%, about 0.02%, about
0.03%, about 0.04%, about 0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.09%,
about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%,
about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%,
about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, or about 2.0%. In an
embodiment, a steroid and/or NSAID is present in the composition or preparation at a
level of about 0.001% or less, about 0.002% or less, about 0.003% or less, about 0.004%
or less, about 0.005% or less, about 0.006% or less, about 0.007% or less, about 0.008% or
less, about 0.009% or less, about 0.01% or less, about 0.02% or less, about 0.03% or less,
about 0.04% or less, about 0.05% or less, about 0.06% or less, about 0.07% or less, about
0.08% or less, about 0.09% or less, about 0.1% or less, about 0.2% or less, about 0.3% or
less, about 0.4% or less, about 0.5% or less, about 0.6% or less, about 0.7% or less, about
0.8% or less, about 0.9% or less, about 1.0% or less, about 1.1% or less, about 1.2% or
less, about 1.3% or less, about 1.4% or less, about 1.5% or less, about 1.6% or less, about
1.7% or less, about 1.8% or less, about 1.9% or less, or about 2.0% or less. In an
embodiment, a steroid and/or NSAID is present in the composition or preparation at a
level of about 0.001% or more, about 0.002% or more, about 0.003% or more, about
0.004% or more, about 0.005% or more, about 0.006% or more, about 0.007% or more,
about 0.008% or more, about 0.009% or more, about 0.01% or more, about 0.02% or
more, about 0.03% or more, about 0.04% or more, about 0.05% or more, about 0.06% or
more, about 0.07% or more, about 0.08% or more, about 0.09% or more, about 0.1% or
more, about 0.2% or more, about 0.3% or more, about 0.4% or more, about 0.5% or more,
about 0.6% or more, about 0.7% or more, about 0.8% or more, about 0.9% or more, about
1.0% or more, about 1.1% or more, about 1.2% or more, about 1.3% or more, about 1.4%
or more, about 1.5% or more, about 1.6% or more, about 1.7% or more, about 1.8% or
more, about 1.9% or more, or about 2.0% or more.
The compositions disclosed herein can be administered as solutions, suspensions,
emulsions (dispersions), gels, creams, or ointments in a suitable ophthalmic vehicle. In
any of the compositions of this disclosure for topical administration, such as topical
administration to the eye, the mixtures are preferably formulated as aqueous solutions at a
pH of 3.5 to 6.5. Preferentially the pH is adjusted to between 4 and 5. This pH range may
be achieved by the addition of acids/bases to the solution.
In an embodiment, an ophthalmic composition may comprise an optional co-
solvent. In another embodiment, the solubility of the components of the present
compositions may be enhanced by a surfactant or other appropriate co-solvent in the
composition. Such co-solvents or surfactants include polysorbate -20, -60, and -80, a
polyoxyethylene/polyoxypropylene surfactant (e.g. Pluronic F-68, F-84 and P-103),
cyclodextrin, tyloxapol, PEG 35 Castor oil (Cremophor EL), polyoxyl 40 Stearate (Myrj
52), other agents known to those skilled in the art, or a combination thereof. Typically,
such co-solvents are present at a level of from about 0.01% to about 2% by weight. In an
embodiment, a co-solvent is present at a level of about 0.01%, about 0.02%, about 0.03%,
about 0.04%, about 0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.09%, about
0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about
0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about
1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, or about 2.0%.
In an embodiment, a composition may comprise an optional agent that can increase
viscosity. As will be understood by the skilled artisan when armed with the present
disclosure, it may be desirable to increase viscosity above that of a simple aqueous
solution in order to increase ocular absorption of the active compound, to decrease
variability in dispensing the formulation, to decrease physical separation of components of
a suspension or emulsion of the formulation and/or to otherwise improve the ophthalmic
formulation. Such viscosity-enhancing agents include, but are not limited to, polyvinyl
alcohol, polyvinyl pyrrolidone, methyl cellulose, hydroxypropylmethyl cellulose,
hydroxyethyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, other agents
known to those skilled in the art, or any combination thereof. Such agents are typically
employed at a level of from about 0.01% to about 2% by weight. In an embodiment, such
optional agents are present at about 0.01%, about 0.02%, about 0.03%, about 0.04%, about
0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.09%, about 0.1%, about 0.2%,
about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%,
about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%,
about 1.7%, about 1.8%, about 1.9%, or about 2.0%.
In another aspect, bioadhesive agents may comprise the compositions, in order to
increase the retention time of the drug gradient over a biological substrate. The
bioadhesive agents include, but are not limited to, polyvinylpyrrolidone (PVP), xanthan
gum, locust bean gum, acacia gum, hydroxypropyl methylcellulose (HPMC), sodium
alginate, pectin, gelatin, carbomer, polyvinylalcohol, gellan gum, tragacanth, acacia, and
sodium carboxymethyl cellulose, as well as other agents known to those skilled in the art,
or any combination thereof. In yet another embodiment, compositions of the invention
may comprise viscoelastic agents such as methyl cellulose, carboxymethyl cellulose,
hydroxyethyl cellulose, polyvinyl alcohol, dextran, chondroitin sulfate and salts thereof,
and hyaluronic acid and salts thereof.
Compositions disclosed herein may be buffered or non-buffered. The skilled
artisan will understand when a PVP-I composition may require buffering, or when a
method of use will benefit from a buffered PVP-I composition.
In an embodiment, a composition disclosed herein may consist essentially of PVP-
I. In an embodiment, a composition disclosed herein may consist essentially of PVP-I and
one or more steroids. In an embodiment, a composition disclosed herein may consist
essentially of PVP-I and one or more NSAIDS. In an embodiment, a composition
disclosed herein may consist essentially of PVP-I and one or more steroids and one or
more NSAIDS. In an aspect, a composition consisting essentially of PVP-I, PVP-I plus
one or more steroids, PVP-I plus one or more NSAIDS, or PVP-I plus one or more
steroids and one or more NSAIDS does not contain any other components that materially
affect the basic and novel characteristics of the composition. In another aspect, a
composition consisting essentially of PVP-I, PVP-I plus one or more steroids, PVP-I plus
one or more NSAIDS, or PVP-I plus one or more steroids and one or more NSAIDS does
not contain any other components that materially affect the basic and novel characteristics
of the method of use of the composition. In yet another aspect, a composition consisting
essentially of PVP-I, PVP-I plus one or more steroids, PVP-I plus one or more NSAIDS,
or PVP-I plus one or more steroids and one or more NSAIDS does not contain any other
components that materially affect the basic and novel characteristics of the composition,
but may affect the method of use of the composition such that the composition may have
the same basic effect on a subject, but that the composition may provide one or more of
fewer side effects, less severe side effects, increased efficacy, decreased toxicity, more
rapid treatment of the adverse health condition, more complete treatment of the adverse
health condition, and the ability to use or administer the composition in conjunction with
one or more other compositions.
It will be understood that the balance of a composition, after addition of the one or
more components specified herein, may be water, or other suitable solvent or carrier.
Other components necessary to prepare a suitable pharmaceutical composition can also be
included in addition to the one or more components specified herein.
Methods
In an embodiment, compositions disclosed herein are useful for preparation of and
use as pharmaceutical compositions. In another embodiment, compositions disclosed
herein are useful for preparation of and use as compositions other than pharmaceutical
compositions.
Disclosed herein is a method for treating an eye disorder, or a microorganism
infection of at least one tissue of the eye, comprising the step of administering one or more
doses of a composition disclosed herein to the eye. In an embodiment, compositions
disclosed herein are useful for preparation of and use as ophthalmic compositions. In an
aspect, a composition of the invention is useful in the treatment of infections of the
conjunctiva and cornea. In another aspect, the broad spectrum antimicrobial activity of
povidone-iodine enables a composition of the invention to be used to treat ocular
conjunctival or corneal infection caused by mycobacteria, viruses, fungi, and amoeba.
Additionally the composition is useful in the infectious prophylaxis of patients recovering
from ophthalmic surgery.
In an embodiment, an ophthalmic composition is provided that is suitable for
topical administration to an eye, effective for treatment and/or prophylaxis of a
microorganism infection or a disorder of at least one tissue of the eye. Prophylaxis may be,
for example, prophylaxis from infection following surgery, prophylaxis from infection
after birth for the newborn, or prophylaxis from accidental contact with contaminating
material. Accidental contact with contaminating material may occur, for example, during
surgery or through close contact with a contaminated family member or co-worker.
In an embodiment, an ophthalmic composition may further comprise one or more
of (1) a penetration enhancer which enhances the penetration of povidone-iodine into the
tissues of the eye (this may be a topical anesthetic) (2) a co-solvent or a nonionic surface
agent - surfactant, which, for example, may be about 0.01% to 2% by weight; (3) a
viscosity increasing agent, which, for example, may be about 0.01% to 2% by weight; and
(4) a suitable ophthalmic vehicle.
The ophthalmic composition may be in the form of a solution, a suspension, an
emulsion, a preparation, an ointment, a cream, a gel, or a controlled-release/sustain-release
vehicle. By way of a non-limiting example, the composition may be in the form of a
contact lens solution, eyewash, eyedrop, and the like.
In an aspect, the ophthalmic composition may be used for treatment and/or
prophylaxis of a microorganism infection. The microorganism may be a bacterium, a
virus, a fungus, or an amoeba, a parasite, or a combination thereof. In an embodiment, the
bacteria may be a mycobacterium.
In an aspect, an ophthalmic composition may be used to treat a disorder such as,
but not limited to, conjunctivitis, corneal abrasion, ulcerative infectious keratitis, epithelial
keratitis, stromal keratitis, herpesvirus-related keratitis, ocular surface irregularity, tear
deficiency, dry syndrome, meibomian gland dysfunction, blepharitis and uveitis. In
another aspect, an ophthalmic composition may be used for prophylaxis of disorders such
as conjunctivitis, corneal abrasion, ulcerative infectious keratitis, epithelial keratitis,
stromal keratitis, herpesvirus-related keratitis, ocular surface irregularity, tear deficiency,
dry syndrome, meibomian gland dysfunction, blepharitis and uveitis.
Described herein is a method for treating and/or prophylaxis of an eye disorder or a
microorganism infection of at least one tissue of the eye comprising the step of
administering one of more doses of an ophthalmic composition, discussed above, to the
eye. The eye disorder may be, for example, a microorganism infection of at least one
tissue of the eye, conjunctivitis, corneal abrasion, ulcerative infectious keratitis, epithelial
keratitis, stromal keratitis, herpes virus-related keratitis, ocular surface irregularity, tear
deficiency, dry syndrome, meibomian gland dysfunction, and blepharitis. The
microorganism may be bacteria (e.g., mycobacteria), virus, fungi, or amoebae.
In an embodiment, the dose volume administered to a subject may be between
about 10 microliters and about 200 microliters, in another embodiment, between about 20
microliters and 100 microliters, and in another embodiment, between about 50 microliters
and about 80 microliters, or about one drop per eye. Two or more drops may be added to
an eye. Treatment of an eye may be effected by adding a single drop of composition
disclosed herein, or by adding two or more drops, as required to achieve the desired result.
In an embodiment, administration frequency may be between 1 and 24 times a day.
In an embodiment, administration frequency may be between 1 and 48 times a day. In
another embodiment, administration frequency may be between 2 and 24 times a day. In
another embodiment, administration frequency may be between 2 and 4 times a day. In
another embodiment, administration frequency may be twice a day. In another
embodiment, administration frequency may be once a day. In another embodiment,
administration frequency may be less frequent than once a day. In another embodiment,
administration frequency may be on demand, as therapeutic treatment is required or
desired. In another embodiment, administration frequency may be 1, 2, 3, 4, 5, 6, 7, 8, 9,
, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 48, or 96 times a day.
In an embodiment, a composition disclosed herein is used for prophylaxis and/or
treatment of a non-ophthalmic tissue by contacting the tissue with the composition.
Also disclosed herein is a method of treating a mammal having an otic infection,
comprising contacting the ear of the mammal with a composition as disclosed herein. In
an aspect, topical ear medications are not typically able to penetrate the tympanic
membrane thus limiting their usefulness and effectiveness. However, in cases of recurrent
otitis media it is common for physicians to place ventilation tubes through the tympanic
membrane in an effort to reduce the pressure built up in the middle ear and to allow the
middle ear space to “dry out”. Quite frequently, this middle ear space becomes infected
again and because of the placement of the ventilation tube topical preparations have access
to the middle ear infection. Another non-limiting example in which topically applied
medications have access to the middle ear is in chronic suppurative otitis media, in which
a long-standing ear infection has caused the perforation of the tympanic membrane. In
clinical conditions such as these, it is possible to treat the underlying middle ear infection
with topical medications. By way of another non-limiting example, it is possible to treat
other clinical conditions with topical medications. In an embodiment, in cases of otitis
externa in which the tympanic membrane is intact and the infection is solely located
external to the tympanic membrane, topical medications have demonstrated clinical utility
and are used widely.
In an embodiment, disclosed herein is a method of using a topical pharmaceutical
composition for treating and relieving the symptoms of ear, including, but not limited to,
otitis interna, otitis media and otitis externa (both acute and chronic). In an embodiment,
the compositions comprise PVP-I in an amount effective to reduce the growth of infection
causing microbes and a pharmaceutically acceptable carrier therefor. In an embodiment,
PVP-I is present in an otic composition in the range of about 0.1%-10%, about 0.5%-5%,
or about 1% to about 3%. In an embodiment, PVP-I is present in an otic composition at
about 2%. Other suitable PVP-I concentrations are set forth elsewhere herein. In an
embodiment, the otic compositions may additionally comprise a steroid, such as, but not
limited to, dexamethasone.
Methods of treating a mammal for an otic infection use the compounds disclosed
herein. In compositions for topical administration, the mixtures are preferably formulated
as aqueous solutions at a pH of 3.5 to 6.5. In an embodiment, the pH is adjusted to
between 4 and 5. This pH range may be achieved by the inclusion of suitable acids/bases
in the composition.
In methods of treating a mammal for an otic infection using the compounds
disclosed herein, a topical composition may comprise one or more of an excipient, an
antimicrobial agent, a preservative, a cosolvent, a surfactant, a viscosity agent, and/or a
bioadhesive agent, as set forth in detail elsewhere herein. In an embodiment, an otic
pharmaceutical preparation is a partially-alcoholic preparation. In an aspect, an otic
composition is a zinc acetate composition. In another aspect, an otic composition is an
acetic acid composition.
As will be understood by the skilled artisan, inclusion of a percentage of alcohol in
the preparation will aid in the solubility of the components, including the steroid and the
PVP-I. The alcohol component will also serve as a dehydrating component for the surface
to which the preparation is applied. Alcohols useful in the invention include methanol,
ethanol, and isopropanol, among others.
In other embodiments, compositions and methods disclosed herein are useful for
treatment of other parts of the body, including the nasal passages, sinuses, the skin and the
vagina. In another embodiment, compositions and methods disclosed herein are useful for
treatment of external parts of the body. In an embodiment, PVP-I is present in a
composition for treatment of other parts of the body in the range of about 0.1%-12.5% or
about 1% to about 10%. Other suitable PVP-I concentrations are set forth elsewhere
herein. In an embodiment, compositions for treatment of other parts of the body may
additionally comprise a steroid, such as, but not limited to, dexamethasone.
In an embodiment, compositions and methods disclosed herein are useful for
treating a human. In an embodiment, the human is an adult. In another embodiment, the
human is a child. In an embodiment, compositions and methods disclosed herein are
pediatric compositions, and methods of pediatric treatment. In an aspect, a pediatric
composition contains components, including PVP-I, at concentrations suitable for treating
a child. By way of a non-limiting example, a pediatric composition may comprise a lower
concentration of PVP-I, steroid, or NSAID, than a comparable composition for use in an
adult. In an embodiment, an NSAID is used in place of a steroid in a pediatric
composition. Described herein is a method for pediatric treatment, comprising treatment
of a patient using a composition comprising components, including PVP-I, at
concentrations suitable for treating a child. In an embodiment, such concentrations are
lower than the concentrations of the same components that would be used to treat an adult.
Described herein is a method for pediatric treatment, comprising treatment of a patient
using a composition comprising PVP-I and an NSAID.
In an embodiment, disclosed herein is a method of preparing a composition
comprising PVP-I at a starting concentration between about 0.4% and about 12.5% by
weight, wherein after a period of one month after preparing the composition, the PVP-I
concentration is at least 98% of the PVP-I starting concentration, and after a period of six
months after preparing the composition, the PVP-I concentration is at least 96% of the
PVP-I starting concentration. In another embodiment, disclosed herein is a method of
preparing a composition comprising PVP-I at a starting concentration between about
0.001% and about 0.6% by weight, wherein after a period of one month after preparing the
composition, the PVP-I concentration is at least 93% of the PVP-I starting concentration,
and after a period of six months after preparing the composition, the PVP-I concentration
is at least 93% of the PVP-I starting concentration.
In an embodiment, the method of preparing a PVP-I composition according to the
disclosure herein further comprises the addition of one or more steroids including, but not
limited to, dexamethasone, dexamethasone alcohol, dexamethasone sodium phosphate,
fluorometholone acetate, fluorometholone alcohol, loteprednol etabonate, medrysone,
prednisolone acetate, prednisolone sodium phosphate, difluprednate, rimexolone,
hydrocortisone, hydrocortisone acetate, lodoxamide tromethamine, and any combinations
thereof. The steroid may be used any form, and in various modified forms such as acetate
forms, and sodium phosphate forms, sodium salts, and the like. In an embodiment, a
pharmaceutically acceptable salt of the steroid can be used in the method of preparation.
In an embodiment, the method of preparing a PVP-I composition according to the
disclosure herein further comprises the addition of one or more NSAIDS including, but
not limited to, amfenac, bromfenac, ketotifen fumarate, diclofenac, diclofenac sodium,
flurbiprofen sodium, ketorlac, ketorlac tromethamine, suprofen, celecoxib, naproxen,
rofecoxib, or a derivative or combination thereof. Pharmaceutically-acceptable salts of
NSAIDS are also contemplated herein.
In another embodiment, a method of making a PVP-I composition further
comprises adding one or more components required to prepare a suitable pharmaceutical
composition. Such components, described elsewhere herein, include, but are not limited
to bioadhesive agents and excipients, as well as components required to prepare the
composition as a solution, suspension, emulsion (dispersion), gel, cream, or ointment, or
other form for administration.
In an embodiment, a method of making a PVP-I composition comprises storing the
prepared composition for a period of time before use to allow stabilization and/or
degradation to occur. In an embodiment, the prepared composition is stored for about 1
hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 12
hours, about 18 hours, or about 24 hours before use. In an embodiment, the prepared
composition is stored for about 1 day, about 2 days, about 3 days, about 4 days, about 5
days, about 6 days, or about 7 days before use. In an embodiment, the prepared
composition is stored for about 1 week, about 2 weeks, about 3 weeks, about 4 weeks,
about 5 weeks, about 6 weeks, about 7 weeks, or about 8 weeks before use. In an
embodiment, the prepared composition is stored for about 1 month, about 2 months, about
3 months, about 4 months, about 5 months, about 6 months, about 9 months, or about 12
months before use. In an embodiment, the storage is accompanied by agitation and/or
stirring of the composition. In another embodiment, the storage is accompanied by
application of heat to the composition.
The invention is further described by the following examples. It should be
recognized that variations based on the inventive features are within the skill of the
ordinary artisan, and that the scope of the invention should not be limited by the examples.
To properly determine the scope of the present disclosure, an interested party should
consider the claims herein, and any equivalent thereof. All patents, patent applications,
and references cited herein are hereby incorporated by reference in their entirety.
EXAMPLES
Example 1: Stability of 0.4% PVP-I Composition
Several preparations of 0.4% PVP-I were stored at 25° C for one month, three
months, and six months. After one month, the 0.4% PVP-I preparation retained 93.75% of
the starting PVP-I concentration. After three months, the 0.4% PVP-I preparation retained
93.27% of the starting PVP-I concentration. After six months, the 0.4% PVP-I preparation
retained 93.22% of the starting PVP-I concentration.
Example 2: Stability of 1.0% PVP-I Composition
Several preparations of 1.0% PVP-I were stored at 25° C for one month, three
months, and six months. After one month, the 1.0% PVP-I preparation retained 98.0% of
the starting PVP-I concentration. After three months, the 1.0% PVP-I preparation retained
97.0% of the starting PVP-I concentration. After six months, the 1.0% PVP-I preparation
retained 96.0% of the starting PVP-I concentration.
Example 3: Stability of PVP-I in the Presence of Dexamethasone
Several preparations of PVP-I were stored at various temperatures for periods of
one month, three months, six months and twelve months. The results are shown in Table
1. The starting concentration of PVP-I, at the time of preparation of the composition, is
referenced as 100 percent. The concentrations at each time point are given as percent of
the initial concentration. Formulation A: 0.1% dexamethasone + 0.4% PVP-I;
Formulation B: 0.1% dexamethasone + 0.48% PVP-I; Formulation C: 0.1%
dexamethasone + 0.6% PVP-I; Formulation D: 0.1% dexamethasone + 1.0% PVP-I.
Table 1: Stability of PVP-I in the Presence of Dexamethasone
Formulation Storage Initial 1 3 3 6 12
Temperature Concentration Month Months Months Months Months
A 5°C 100% 94.9 96.8 98.6 94.7
A 25°C 100% 93.8 92.4 91.3 87.6 83.4
B 5°C 100% 97.1 96.1 96.9 95.0
B 25°C 100% 95.7 90.5 90.1 88.8 84.9
C 5°C 100% 95.4 95.7 9732 97.3
C 25°C 100% 93 92.4 8839 88.6
D 5°C 100% 99.2 99.1 100.5
D 25°C 100% 98.5 97.1 96.1 93.4
Claims (12)
1. A composition suitable for topical administration, comprising a mixture of a) povidone-iodine (PVP-I) at a starting concentration between about 0.001% and about 12.5% by weight; and b) at least one non-steroidal anti-inflammatory (NSAID), which is amfenac or a salt thereof.
2. The composition of claim 1, wherein the composition is an ophthalmic composition.
3. The composition of claim 1 or 2, wherein the NSAID is present at a concentration of about 0.001% to about 10% by weight.
4. The composition of any one of claims 1-3, wherein the NSAID is present at a concentration of about 0.1% by weight.
5. The composition of any one of claims 1-4, wherein the PVP-I concentration is about 12.5% by weight.
6. The composition of any one of claims 1-4, wherein the PVP-I concentration is about 0.005% by weight.
7. The composition of any one of claims 1-4, wherein the PVP-I concentration is about 0.001% by weight.
8. Use of PVP-I and at least one non-steroidal anti-inflammatory (NSAID), which is amfenac or a salt thereof, for the manufacture of a medicament for treating an eye disorder or a microorganism infection of at least one tissue of the eye, wherein the starting concentration of the PVP-I is between about 0.001% and about 12.5% by weight.
9. The use of claim 8, wherein the medicament is a composition as defined in any one of claims 2-7.
10. Use of a composition of any one of claims 1-7 for the manufacture of a medicament for treating an eye disorder or a microorganism infection of at least one tissue of the eye.
11. A composition as claimed in any one of claims 1-7 substantially as herein described with reference to any example thereof.
12. Use as claimed in any one of claims 8-10 substantially as herein described with reference to any example thereof.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161535667P | 2011-09-16 | 2011-09-16 | |
US61/535,667 | 2011-09-16 | ||
NZ72042012 | 2012-09-14 |
Publications (2)
Publication Number | Publication Date |
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NZ738063A NZ738063A (en) | 2019-08-30 |
NZ738063B2 true NZ738063B2 (en) | 2019-12-03 |
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