U.S. patent application number 17/563542 was filed with the patent office on 2022-04-21 for compositions and methods for treating an infection.
This patent application is currently assigned to CMPD Licensing, LLC. The applicant listed for this patent is CMPD Licensing, LLC. Invention is credited to Jay Richard Ray, II.
Application Number | 20220117988 17/563542 |
Document ID | / |
Family ID | 1000006055952 |
Filed Date | 2022-04-21 |
United States Patent
Application |
20220117988 |
Kind Code |
A1 |
Ray, II; Jay Richard |
April 21, 2022 |
COMPOSITIONS AND METHODS FOR TREATING AN INFECTION
Abstract
The present application relates to compounded compositions,
methods of making compounded compositions, and methods of using
compounded compositions. For example, disclosed herein are
compounded compositions and methods of making compounded
compositions comprising one or more anti-infective agents such as
streptomycin and one or more of colistimethate, clindamycin, or
mupirocin.
Inventors: |
Ray, II; Jay Richard;
(Conroe, TX) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
CMPD Licensing, LLC |
Conroe |
TX |
US |
|
|
Assignee: |
CMPD Licensing, LLC
Conroe
TX
|
Family ID: |
1000006055952 |
Appl. No.: |
17/563542 |
Filed: |
December 28, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16846983 |
Apr 13, 2020 |
11207336 |
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17563542 |
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15668449 |
Aug 3, 2017 |
10617703 |
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16846983 |
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15597936 |
May 17, 2017 |
10105342 |
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15668449 |
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14566313 |
Dec 10, 2014 |
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15597936 |
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15440800 |
Feb 23, 2017 |
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15597936 |
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14975172 |
Dec 18, 2015 |
9707229 |
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15440800 |
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14819342 |
Aug 5, 2015 |
10973804 |
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14975172 |
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62298994 |
Feb 23, 2016 |
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62298991 |
Feb 23, 2016 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 31/7036 20130101;
A61K 31/7048 20130101; A61K 9/06 20130101; A61K 45/06 20130101;
A61K 31/496 20130101; A61K 31/65 20130101; A61K 38/12 20130101;
A61K 9/0043 20130101; A61K 31/7056 20130101; A61K 31/351 20130101;
A61K 9/48 20130101; A61K 9/08 20130101; A61K 31/5383 20130101; A61K
31/506 20130101; A61K 9/14 20130101; A61K 31/431 20130101; A61K
9/0019 20130101; A61K 9/0014 20130101 |
International
Class: |
A61K 31/7036 20060101
A61K031/7036; A61K 38/12 20060101 A61K038/12; A61K 31/7056 20060101
A61K031/7056; A61K 31/351 20060101 A61K031/351; A61K 31/5383
20060101 A61K031/5383; A61K 9/14 20060101 A61K009/14; A61K 9/48
20060101 A61K009/48; A61K 9/00 20060101 A61K009/00; A61K 9/08
20060101 A61K009/08; A61K 9/06 20060101 A61K009/06; A61K 45/06
20060101 A61K045/06; A61K 31/65 20060101 A61K031/65; A61K 31/7048
20060101 A61K031/7048; A61K 31/431 20060101 A61K031/431; A61K
31/506 20060101 A61K031/506; A61K 31/496 20060101 A61K031/496 |
Claims
1. A method of treating or preventing a bacterial infection of a
subject, the method comprising: formulating a treatment composition
comprising combining a diluent, a dry powder comprising at least
streptomycin, and one or more addition anit-infectives selected
from colistimethate, clindamycin, mupirocin, and combination
thereof; and contacting a body surface of a subject that is
infected or suspected to be infected with the treatment composition
to topically deliver the one or more anti-infective agents to the
body surface.
2. The method of claim 1, wherein formulating the treatment
composition further comprises opening a capsule comprising at least
the streptomycin to release the dry powder for combining with the
diluent.
3. The method of claim 2, wherein the dry powder further xylitol
and poloxamers.
4. The method of claim 2, wherein the dry powder contained in the
capsule also contains one or more of the one or more additional
anti-infective agents.
5. The method of claim 4, wherein the dry powder further xylitol
and poloxamers.
6. The method of claim 1, wherein the compounded composition
comprises between about 1% and about 10% streptomycin by
weight.
7. The method of claim 1, wherein the contacting the body surface
comprises contacting the body surface with a suitable amount of the
treatment composition to topically deliver between 25 mg and 1 gm
of streptomycin per day.
8. The method of claim 1, wherein the one or more additional
anti-infective agents are combined at a ratio between about 1:3 and
about 1:10 by weight with respect to the streptomycin.
9. The method of claim 8, wherein the diluent comprises a cream,
ointment, emulsion, or gel.
10. The method of claim 9, wherein the diluent comprises a sterile
aqueous solution, and contacting the body surface comprises
nebulizing the treatment composition to deliver the streptomycin
and one or more additional anti-infectives to a surface of a lung
of the subject.
11. The method of claim 1, wherein the one or more additional
anti-infective agents comprise mupirocin, and formulating the
treatment composition comprises combining the streptomycin with
mupirocin ointment.
12. A homogenous compounded ointment for the treatment or
prevention of a bacterial infection of a subject treatment, the
compounded ointment comprising: streptomycin sulfate for injection
and one or more additional anti-infective agents selected from
colistimethate, clindamycin, mupirocin, and combinations thereof in
an ointment base, wherein the compounded ointment comprises between
about 1% and 10% streptomycin by weight.
13. The compounded ointment of claim 12, wherein the additional
anti-infective agent is present in the compounded ointment at a
weight ratio between about 1:3 and about 1:10 by weight with
respect to streptomycin of the streptomycin sulfate.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a continuation of U.S. patent
application Ser. No. 16/846,983, filed April 13, 2020, now U.S.
Pat. No. 11,207,336, which is a continuation of U.S. patent
application Ser. No. 15/668,449, filed Aug. 3, 2017, now U.S. Pat.
No. 10,617,703, which is a continuation-in-part application of U.S.
patent application Ser. No. 15/597,936, filed 17 May 2017, now U.S.
Pat. No. 10,105,342, and U.S. patent application Ser. No.
14/566,313, filed 10 Dec. 2014, abandoned, each of which is
incorporated herin by reference in its entirety. U.S. patent
application Ser. No. 15/597,936 is a continuation-in-part
application of U.S. patent application Ser. No. 15/440,800, filed
23 Feb. 2017, abandoned, U.S. patent application Ser. No.
14/975,172, filed 18 Dec. 2015, now U.S. Pat. No. 9,707,229, and
U.S. patent application Ser. No. 14/819,342, filed 5 Aug. 2015, now
U.S. Pat. No. 10,973,804, each of which is incorporated herein by
reference in its entirety. U.S. patent application Ser. No.
15/440,800 claims priority to U.S. Provisional Patent Application
No. 62/298,991, filed 23 Feb. 2016, and to U.S. Provisional Patent
Application No. 62/298,994, filed 23 Feb. 2016, each of which is
incorporated herein by reference in its entirety.
BACKGROUND
[0002] The body normally serves as host for a variety of bacteria
and fungi. Most of the time, the balance between the body as host
and the microorganisms is maintained. However, there are times when
the physiological, biochemical, and/or environmental conditions
permit the microorganisms to tip that balance, thereby causing an
infection.
[0003] Despite advances in the understanding of the pathology of
bacterial infections and fungal infections, there is still a need
for compositions and methods that efficiently treat or prevent the
progression and reoccurrence of bacterial infections and fungal
infections that affect the skin, the respiratory system, or the
feet.
SUMMARY
[0004] In one aspect, a method of treating or preventing a
bacterial infection of a subject includes formulating a treatment
composition comprising combining a diluent and a dry powder,
wherein the dry powder comprises one or more anti-infective agents
including at least a first anti-infective agent comprising
streptomycin. The method may also include contacting a body surface
of a subject that is infected or suspected to be infected with the
treatment composition to topically deliver the one or more
anti-infective agents to the body surface.
[0005] In various embodiments, the one or more anti-infective
agents comprise a second anti-infective agent comprising
colistimethate, clindamycin, mupirocin, levofloxacin, or
combination thereof. Formulating the treatment composition may
further include opening a capsule comprising at least the first
anti-infective agent to release the dry powder of at least the
first anti-infective agent for combining with the diluent. The
capsule may include a dry powder including both the first
anti-infective agent and the second anti-infective agent. In one
embodiment, the compounded composition comprises between about 1%
and about 10% streptomycin by weight. Contacting the body surface
of the subject may include contacting the body surface with a
suitable amount of the treatment composition to topically deliver
between 25 mg and 1 gm of streptomycin per day.
[0006] In various embodiments, the second anti-infective agent is
present in the dry powder at a ratio between about 1:3 and about
1:10 with respect to the first anti-infective agent. In one
example, the diluent comprises a cream, ointment, emulsion, or gel.
In one configuration, the diluent comprises a sterile aqueous
solution, and contacting the body surface comprises nebulizing the
treatment composition to deliver the streptomycin to a surface of a
lung of the subject. In another example, the diluent comprises a
sterile aqueous solution, and contacting the body surface comprises
nebulizing the treatment composition to deliver the streptomycin to
a surface of a lung of the subject. In one example, the body
surface comprises broken tissue, the diluent is a sterile aqueous
diluent, and the treatment composition comprises a wound irrigation
solution. In another example, the body surface comprises broken
tissue, the diluent comprises a dry powder diluent, and the
treatment composition comprises a wound powder. In one example, the
diluent comprises an aqueous solution and contacting the body
surface comprises contacting foot of the subject with the treatment
composition in a foot bath.
[0007] In one embodiment, combining the diluent and dry powder
comprises combining a dry powder of streptomycin sulfate for
injection with the diluent. In another embodiment, formulating the
treatment composition further comprises combining an additional
anti-infective agent comprising a mupirocin ointment with the dry
powder and diluent.
[0008] In another aspect, a homogenous compounded ointment for the
treatment or prevention of a bacterial infection of a subject
treatment includes streptomycin sulfate for injection in an
ointment base and the compounded ointment comprises between about
1% and 10% streptomycin by weight.
[0009] In various embodiments, the compounded ointment further
comprising an additional anti-infective agent comprising an
antibacterial, antifungal, or combination thereof. The additional
anti-infective agent may include colistimethate, clindamycin,
mupirocin, levofloxacin, or combination thereof. In one example,
the additional anti-infective agent is present in the compounded
ointment at a weight ratio between about 1:3 and about 1:10 with
respect to the streptomycin of the streptomycin sulfate.
[0010] In still another aspect, a kit for treating or preventing a
bacterial infection of a subject may include a capsule containing a
dry powder including at least streptomycin sulfate for injection
and a diluent for combining with the dry powder to formulate a
topical treatment composition to administer to a body surface that
is infected or suspected to be infected. The diluent may comprise
an ointment, cream, gel, emulsion, aqueous solution, or powder.
[0011] In one embodiment, the kit comprises an amount of dry powder
and diluent for preparation of a suitable amount of treatment
composition to topically deliver between 25 mg and 1 gm of
streptomycin in one day. In various embodiments, the dry powder
further includes an additional anti-infective agent comprising
colistimethate, clindamycin, mupirocin, levofloxacin, or
combination thereof. In one example, the additional anti-infective
agent is present in the dry powder at a weight ratio between about
1:3 and about 1:10 with respect to streptomycin of the streptomycin
sulfate. In another example, the diluent may include a sterile
aqueous solution, and the topical treatment composition may
comprise a nebulization solution to deliver the streptomycin and
additional anti-infective to a surface of a lung of the subject. In
still another example, the diluent may comprise a sterile aqueous
solution, and the topical treatment composition comprises a wound
irrigation solution to deliver the streptomycin and additional
anti-infective to a broken tissue surface of the subject. In yet
another example, the diluent comprises a dry powder and the topical
treatment composition comprises a wound powder. In still yet
another example, the diluent comprises an aqueous solution and the
topical treatment composition a foot bath solution.
DETAILED DESCRIPTION
[0012] The present invention can be understood more readily by
reference to the following detailed description of the invention
and the Examples included therein.
[0013] Before the present compounds, compositions, articles,
systems, devices, and/or methods are disclosed and described, it is
to be understood that they are not limited to specific synthetic
methods unless otherwise specified, or to particular reagents
unless otherwise specified, as such may, of course, vary. It is
also to be understood that the terminology used herein is for the
purpose of describing particular aspects only and is not intended
to be limiting. Although any methods and materials similar or
equivalent to those described herein can be used in the practice or
testing of the present invention, example methods and materials are
now described.
[0014] All publications mentioned herein are incorporated herein by
reference to disclose and describe the methods and/or materials in
connection with which the publications are cited. The publications
discussed herein are provided solely for their disclosure prior to
the filing date of the present application. Nothing herein is to be
construed as an admission that the present invention is not
entitled to antedate such publication by virtue of prior
invention.
A. Definitions
[0015] As used in the specification and the appended claims, the
singular forms "a", "an", and "the" include plural referents unless
the context clearly dictates otherwise.
[0016] The phrase "consisting essentially of" limits the scope of a
claim to the recited components in a composition or the recited
steps in a method as well as those that do not materially affect
the basic and novel characteristic or characteristics of the
claimed composition or claimed method. The phrase "consisting of"
excludes any component, step, or element that is not recited in the
claim. The phrase "comprising" is synonymous with "including",
"containing", or "characterized by", and is inclusive or
open-ended. "Comprising" does not exclude additional, unrecited
components or steps.
[0017] As used herein when referring to any numerical value, the
term "about" means a value falling within a range that is .+-.10%
of the stated value.
[0018] Ranges can be expressed herein as from "about" one
particular value, and/or to "about" another particular value. When
such a range is expressed, a further aspect includes from the one
particular value and/or to the other particular value. Similarly,
when values are expressed as approximations, by use of the
antecedent "about," it will be understood that the particular value
forms a further aspect. It will be further understood that the
endpoints of each of the ranges are significant both in relation to
the other endpoint and independently of the other endpoint. It is
also understood that there are a number of values disclosed herein,
and that each value is also herein disclosed as "about" that
particular value in addition to the value itself. For example, if
the value "10" is disclosed, then "about 10" is also disclosed. It
is also understood that each unit between two particular units are
also disclosed. For example, if 10 and 15 are disclosed, then 11,
12, 13, and 14 are also disclosed.
[0019] References in the specification and concluding claims to
parts by weight of a particular element or component in a
composition denotes the weight relationship between the element or
component and any other elements or components in the composition
or article for which a part by weight is expressed. Thus, in a
compound containing 2 parts by weight of component X and 5 parts by
weight component Y, X and Y are present at a weight ratio of 2:5,
and are present in such ratio regardless of whether additional
components are contained in the compound.
[0020] As used herein, the terms "optional" or "optionally" means
that the subsequently described event or circumstance can or cannot
occur, and that the description includes instances where said event
or circumstance occurs and instances where it does not. In an
aspect, a disclosed method can optionally comprise one or more
additional steps, such as, for example, repeating an administering
step or altering an administering step.
[0021] As used herein, the term "subject" refers to the target of
administration, e.g., a human being. The term "subject" also
includes domesticated animals (e.g., cats, dogs, etc.), livestock
(e.g., cattle, horses, pigs, sheep, goats, etc.), and laboratory
animals (e.g., mouse, rabbit, rat, guinea pig, fruit fly, etc.).
Thus, the subject of the herein disclosed methods can be a
vertebrate, such as a mammal, a fish, a bird, a reptile, or an
amphibian. Alternatively, the subject of the herein disclosed
methods can be a human, non-human primate, horse, pig, rabbit, dog,
sheep, goat, cow, cat, guinea pig, or rodent. The term does not
denote a particular age or sex. Thus, adult and child subjects, as
well as fetuses, whether male or female, are intended to be
covered. In an aspect, a subject can be a human patient. In an
aspect, the subject can have diabetes, can be obese, can be
immunocompromised, can be non-ambulatory, or can have poor blood
flow, or a combination thereof In an aspect, the subject can
routinely wear thick socks or wear heavy boots. In an aspect, the
subject can have been diagnosed with or can be suspected of having
(i) cancer that affects at least a part of the respiratory tract,
(ii) emphysema, (iii) pneumonia, (iv) bronchitis, (v) tuberculosis,
(vi) asthma, or (vii) a combination thereof.
[0022] A subject can have a bacterial infection, be suspected of
having a bacterial infection, or be at risk of developing a
bacterial infection. A subject can have a fungal infection, be
suspected of having a fungal infection, or be at risk of developing
a fungal infection. A subject can have a bacterial infection and a
fungal infection, be suspected of having a bacterial infection and
a fungal infection, or be at risk of developing a bacterial
infection and a fungal infection.
[0023] For example, a subject at risk of developing a bacterial
infection can have, for example, risk factors for developing a
bacterial infection (e.g., have damaged or moist skin, have a
chronic disease, and/or be immunocompromised). For example, a
subject at risk for developing a bacterial infection can be exposed
to a bacterium or bacteria due to employment (e.g., a health care
worker) or due to the prevalence of a bacterium or bacteria at a
specific location (e.g., a hospital).
[0024] For example, a subject at risk of developing a fungal
infection can have, for example, risk factors for developing a
fungal infection (e.g., have damaged or moist skin, have a chronic
disease, and/or be immunocompromised). For example, a subject at
risk for developing a fungal infection can be exposed to a fungus
or fungi due to employment (e.g., a health care worker) or due to
the prevalence of a fungus or fungi at a specific location (e.g., a
hospital).
[0025] A "patient" refers to a subject afflicted with one or more
infections. In an aspect, a patient can refer to a subject that has
been diagnosed with or is suspected of having a bacterial
infection. In an aspect, a bacterial infection or suspected
bacterial infection can affect at least a portion of one or both
feet of the subject, the subject's skin, the subject's respiratory
system, or another appendage, such as at least a portion of one or
both of the subject's hands. In an aspect, a patient can refer to a
subject that has been diagnosed with or is suspected of having a
fungal infection. In an aspect, a fungal infection or suspected
fungal infection can affect at least a portion of one or both feet
of the subject, the subject's skin, the subject's respiratory
system, or another appendage, such as at least a portion of one or
both of the subject's hands.
[0026] As used herein, the term "treatment" refers to the medical
management of a patient with the intent to cure, ameliorate,
stabilize, or prevent a disease, pathological condition, or
disorder (such as, for example, a bacterial infection, a suspected
bacterial infection, a fungal infection, or a suspected fungal
infection, or both). This term includes active treatment, that is,
treatment directed specifically toward the improvement of a
disease, pathological condition, or disorder, and also includes
causal treatment, that is, treatment directed toward removal of the
cause of the associated disease, pathological condition, or
disorder. In addition, this term includes palliative treatment,
that is, treatment designed for the relief of symptoms rather than
the curing of the disease, pathological condition, or disorder;
preventative treatment, that is, treatment directed to minimizing
or partially or completely inhibiting the development of the
associated disease, pathological condition, or disorder; and
supportive treatment, that is, treatment employed to supplement
another specific therapy directed toward the improvement of the
associated disease, pathological condition, or disorder. In various
aspects, the term covers any treatment of a subject, including a
mammal (e.g., a human), and includes: (i) preventing the disease
from occurring in a subject that can be predisposed to the disease
but has not yet been diagnosed as having it; (ii) inhibiting the
disease, i.e., arresting its development; or (iii) relieving the
disease, i.e., causing regression of the disease.
[0027] In an aspect, "treating" means eradicating a bacterial
infection, a fungal infection, a suspected bacterial infection, a
suspected fungal infection, or a combination thereof In an aspect,
treating means reducing the effects of a bacterial infection or a
fungal infection or symptoms of a bacterial infection or a fungal
infection. For example, treating an infection can reduce the
severity of an established infection in a subject by 1%-100% as
compared to a control. In an aspect, treating can refer to a 1%,
2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%,
80%, 90%, or 100% reduction in the severity of an established
bacterial infection or an established fungal infection. For
example, treating an infection can reduce one or more symptoms of
an infection in a subject by 1%-100% as compared to a control. In
an aspect, treating can refer to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%,
9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100% reduction of
one or more symptoms of an established bacterial infection or an
established fungal infection. It is understood that treatment does
not necessarily refer to a cure or complete ablation or eradication
of the bacterial infection, the fungal infection, or both. However,
in an aspect, treatment can refer to a cure or complete ablation or
eradication of the bacterial infection, the fungal infection, or
both.
[0028] As used herein, the term "prevent" or "preventing" refers to
precluding, averting, obviating, forestalling, stopping, or
hindering something from happening, especially by advance action.
It is understood that where reduce, inhibit, or prevent are used
herein, unless specifically indicated otherwise, the use of the
other two words is also expressly disclosed. In an aspect,
preventing a bacterial infection, fungal infection, or both is
intended.
[0029] As used herein, the term "diagnosed" means having been
subjected to a physical examination by a person of skill, for
example, a physician, and found to have a condition that can be
diagnosed or treated by the disclosed compounded composition or the
disclosed methods. For example, "diagnosed with a bacterial
infection" means having been subjected to a physical examination by
a person of skill, for example, a physician, and found to have a
condition that can be treated by a disclosed compounded composition
or a disclosed method. For example, "suspected of having a
bacterial infection" can mean having been subjected to a physical
examination by a person of skill, for example, a physician, and
found to have a condition that can likely be treated by a disclosed
compounded composition or a disclosed method. For example,
"diagnosed with a fungal infection" means having been subjected to
a physical examination by a person of skill, for example, a
physician, and found to have a condition that can likely be treated
by a disclosed compounded composition or a disclosed method. For
example, "suspected of having a fungal infection" can mean having
been subjected to a physical examination by a person of skill, for
example, a physician, and found to have a condition that can be
likely be treated by a disclosed compounded composition or a
disclosed method.
[0030] As used herein, the terms "administering" and
"administration" refer to any method of providing a disclosed
compounded composition or a pharmaceutical preparation comprising a
disclosed compounded composition to a subject. Such methods are
well known to those skilled in the art and include, but are not
limited to: oral administration, transdermal administration,
administration by inhalation, nasal administration, topical
administration, intravaginal administration, ophthalmic
administration, intra-aural administration, intracerebral
administration, rectal administration, sublingual administration,
buccal administration, and parenteral administration, including
injectable such as intravenous administration, intra-arterial
administration, intramuscular administration, and subcutaneous
administration. Administration can be continuous or intermittent.
In various aspects, a disclosed compounded composition, or
anti-infective agent can be administered therapeutically; that is,
administered to treat an existing disease or condition. In further
various aspects, a disclosed compounded composition or a
pharmaceutical preparation comprising a disclosed compounded
composition can be administered prophylactically; that is,
administered for prevention of a disease or condition. In an
aspect, the skilled person can determine an efficacious dose, an
efficacious schedule, and an efficacious route of administration
for a disclosed compounded composition or a disclosed
pharmaceutical preparation comprising a disclosed compounded
composition so as to treat or prevent an infection. In an aspect,
the skilled person can also alter, change, or modify an aspect of
an administering step so as to improve efficacy of a disclosed
compounded composition or a disclosed pharmaceutical preparation
comprising a disclosed compounded composition. In an aspect,
administering means contacting at least a portion of one foot or
both feet of a subject with agitated water comprising a disclosed
compounded composition or a disclosed pharmaceutical preparation
comprising a disclosed compounded composition. In an aspect,
administering means contacting at least a portion of the subject's
skin with disclosed compounded composition or a disclosed
pharmaceutical preparation comprising a disclosed compounded
composition. In an aspect, administering means contacting at least
a portion of the subject's respiratory system with a disclosed
compounded composition or a disclosed pharmaceutical preparation
comprising a disclosed compounded composition. In an aspect,
administering means contacting at least a portion of one foot or
both feet of a subject with agitated water comprising a solution or
suspension comprising a disclosed compounded composition. In an
aspect, administering means contacting at least a portion of the
subject's skin with a solution or suspension comprising a disclosed
compounded composition. In an aspect, administering means
contacting at least a portion of the subject's respiratory system
with a solution or suspension comprising a disclosed compounded
composition.
[0031] As used herein, a "foot bath" refers to a container that can
hold some volume (e.g., about 1.0 liters to about 10 liters) of an
aqueous solution or suspension (e.g., water) and is designed to
physically accommodate at least a portion of one or both feet of a
subject. Foot baths are known to the skilled person. A foot bath
can comprise several features or agents that effect various
functions. For example, a foot bath can comprise one or more lights
or light-emitting devices, a mechanical agitation agent (e.g., one
or more jets or bubble makers) to physically agitate the enclosed
water, a bubble agent to create bubbles within the enclosed water,
a heating agent to heat the enclosed water, a vibration agent to
vibrate the enclosed water (e.g., a high frequency vibration
massage), an infrared device to provide infrared light to a foot or
feet of the subject, a massage agent (e.g., a roller) that provides
massaging contact to at least a portion of one or both feet, a
pedicure agent that can clean or contact a foot or feet with a
pumice, or a combination thereof. In an aspect, a foot bath can
have a water fall element. In an aspect, an agitation agent or an
agitator can be coupled to both a motor and the foot bath. Motors
and agitators are known to the art. In an aspect, a foot bath can
comprise one or more splash guards and other spill-resistant
features to ensure that the water remains enclosed within a
container. A foot bath may also accommodate a subject's calves,
meaning that the container is "deep" so as to allow the enclosed
water to contact both the feet and at least a portion of the calves
of the subject. Several manufacturers market foot baths including
PIBB, Dr. Scholl's, Kendal, Conair (e.g., Model FB5X, FB3, FB27R,
FB30, FB52, etc.), and Brookstone.
[0032] As used herein, a "mixing container" can be a container that
can accommodate one more liquids (such as a diluent, for example)
and one or more disclosed compounded compositions or disclosed
anti-infective agents. A mixing container can have a lid or a
cover, which facilitates the mixing of any liquid with any solid
that has been added to the container. A mixing container can be
used to generate a solution or suspension. In an aspect, a mixing
container can contain about 2 ounces to about 30 ounces. In an
aspect, a mixing container can contain about 6 ounces. In an
aspect, a mixing container can contain about 16 ounces. The art is
familiar with mixing containers and mixing containers are
commercially available.
[0033] As used herein, "modifying the method" can comprise
modifying or changing one or more features or aspects of one or
more steps of a disclosed method. For example, in an aspect, a
method can be altered by changing the amount of a disclosed
compounded composition applied to a subject's skin, or by changing
the frequency of the subject's use of the compounded composition,
or by changing the duration of time that the subject uses the
compounded composition, or a combination thereof In an aspect, a
method can be altered by changing the amount of a disclosed
compounded composition added to a foot bath, by changing the
frequency of the subject's use of the foot bath, or by changing the
duration of time that the subject's foot or feet contact the water
contained within the foot bath, or a combination thereof. The same
modifications can be applied to a method comprising intranasally
administering a disclosed compounded composition or a disclosed
pharmaceutical preparation comprising a disclosed compounded
composition to the subject's nares or topically administering a
disclosed compounded composition or a disclosed pharmaceutical
preparation comprising a disclosed compounded composition to the
subject's skin.
[0034] The term "contacting" as used herein refers to bringing at
least one disclosed compounded compositions or a disclosed
pharmaceutical preparation comprising a disclosed compounded
composition together with a target area or intended target area in
such a manner that the disclosed compounded composition or the
disclosed pharmaceutical preparation comprising a disclosed
compounded composition can exert an effect on the intended target
or targeted area either directly or indirectly. A target or
intended target area can be at least a portion of one or both feet
of a subject or at least portion of the subject's skin or an area
diagnosed with, suspected of having a bacterial infection or a
fungal infection, or susceptible to developing a bacterial
infection or a fungal infection. In an aspect, "contacting" means
to insert or immerse at least a portion of one or both feet of a
subject into the water contained within a foot bath. In an aspect,
"contacting" means topically applying a disclosed compounded
composition to the skin of a subject or intranasally administering
a disclosed compounded composition to the nares of a subj ect.
[0035] The term "mixing" as used in a disclosed method means to
physically combine the recited components so as to achieve a
homogenous compounded composition (which, for example, can be a dry
powder formulation or an ointment). In an aspect, the recited
components can be shaken, or stirred, or agitated so as to achieve
a homogenous compounded composition. In an aspect, "mixing" can
also include sifting the homogenous compounded composition though a
fine mesh strainer. A suitable mixer is a TURBULA.RTM. mixer, which
is able to mix powdery substances with differing specific weights
and particle sizes. The mixing can be generally performed for a
pre-determined amount of time, i.e., for 10 seconds, 20 seconds, 30
seconds, 45 seconds, 1 minute, 5 minute, 10 minutes, 20 minutes, 30
minutes, 40 minutes, 50 minutes, 1 hour, 2 hours, 3 hours, or more.
A person skilled in the art could ascertain without undue
experimentation, the amount of time required to mix the recited
components so as to achieve a homogenous compounded composition. In
an aspect, mixing a powder and an ointment may include combining
one or more powders and the ointment. One or more of the powders or
portions thereof may be wetted prior to addition to the ointment.
Thus, in an aspect, adding, combining, or mixing a powder and an
ointment may include adding, combining, or mixing wetted powder and
the ointment.
[0036] In an aspect, "mixing" can be used to describe the process
of making a solution or suspension by adding one or more disclosed
compounded compositions to a diluent. For example, mixing means to
physically combine a disclosed compounded composition with a
diluent to make a solution or a suspension. Such mixing can occur
in a disclosed mixing container.
[0037] As used herein, "ointment" refers to a homogeneous, viscous
preparation that can be applied to a subject. In aspect, the term
"ointment" can be considered synonymous to a lotion, a cream, an
emulsion, a gel, an emollient, etc. In an aspect, an ointment
comprises a disclosed compounded composition. An ointment can be
applied in a variety of ways, included, for example, but not
limited to, direct topical application to the subject's skin or
contact with skin in an enclosed environment, such as a foot bath.
As used herein, LoxaSperse.TM. refers to an excipient base powder
comprising a blend of micronized xylitol and poloxamers. Such base
compositions are known to those skilled in the art. LoxaSperse.TM.
is manufactured by PCCA (Houston, Tex.) and is used as a chemical
dispersing or solubilizing agent, thereby improving the solubility
and dispersibility of poorly water soluble active pharmaceutical
ingredients (APIs) or agents. LoxaSperse.TM. can be obtained from a
bulk source.
[0038] As used herein, XyliFos.TM. refers to an excipient base
powder comprising xylitol, poloxamer 407, hydroxylpropyl betadex,
and epigallocatechin gallate. XyliFos.TM. is manufactured by PCCA
(Houston, Tex.) and is used as a chemical dispersing or
solubilizing agent, thereby improving the solubility and
dispersibility of poorly water soluble active pharmaceutical
ingredients (APIs) or agents. XyliFos.TM. can be obtained from a
bulk source.
[0039] In an aspect, xylitol can comprise an ointment or can
comprise a dry powder. In an aspect, xylitol can be xylitol NF
(20-80 MESH).
[0040] The term "pharmaceutically acceptable" describes a material
that is not biologically or otherwise undesirable, i.e., without
causing an unacceptable level of undesirable biological effects or
interacting in a deleterious manner. As used herein, the term
"pharmaceutically acceptable carrier" refers to sterile aqueous or
nonaqueous solutions, or suspensions, which may include
dispersions, colloids, or emulsions, as well as sterile powders for
reconstitution into sterile injectable solutions, suspensions just
prior to use. Examples of suitable aqueous and nonaqueous carriers,
diluents, solvents or vehicles include water, ethanol, polyols
(such as glycerol, propylene glycol, polyethylene glycol and the
like), carboxymethylcellulose and suitable mixtures thereof,
vegetable oils (such as olive oil) and injectable organic esters
such as ethyl oleate. These compositions can also contain adjuvants
such as preservatives, wetting agents, emulsifying agents and
dispersing agents. Prevention of the action of microorganisms can
be ensured by the inclusion of various antibacterial and antifungal
agents such as paraben, chlorobutanol, phenol, sorbic acid and the
like. It can also be desirable to include isotonic agents such as
sugars, sodium chloride and the like. Prolonged absorption of the
injectable pharmaceutical form can be brought about by the
inclusion of agents, such as aluminum monostearate and gelatin,
which delay absorption. Injectable depot forms are made by forming
microencapsule matrices of the drug in biodegradable polymers such
as polylactide-polyglycolide, poly(orthoesters) and
poly(anhydrides). Depending upon the ratio of drug to polymer and
the nature of the particular polymer employed, the rate of drug
release can be controlled. Depot injectable formulations are also
prepared by entrapping the drug in liposomes or microemulsions
which are compatible with body tissues. The injectable formulations
can be sterilized, for example, by filtration through a
bacterial-retaining filter or by incorporating sterilizing agents
in the form of sterile solid compositions which can be dissolved or
dispersed in sterile water or other sterile injectable media just
prior to use. Suitable inert carriers can include sugars such as
lactose.
[0041] As used herein, "determining" can refer to measuring or
ascertaining the presence and severity of an infection, such as,
for example, a bacterial infection or a fungal infection that
affects a subject's skin, a subject's respiratory system, or
affects one or more of a subject's appendages (e.g., at least a
portion of one or both feet). Methods and techniques used to
determining the presence and/or severity of an infection are
typically known to the medical arts. For example, the art is
familiar with the ways to identify and/or diagnose the presence,
severity, or both of a bacterial infection, a fungal infection, or
both.
[0042] As used herein, "effective amount" and "amount effective"
can refer to an amount that is sufficient to achieve the desired
result such as, for example, the treatment and/or prevention of a
bacterial infection or a suspected bacterial infection or a fungal
infection or a suspected fungal infection. As used herein, the
terms "effective amount" and "amount effective" can refer to an
amount that is sufficient to achieve the desired an effect on an
undesired condition (e.g., a bacterial or a fungal infection). For
example, a "therapeutically effective amount" refers to an amount
that is sufficient to achieve the desired therapeutic result or to
have an effect on undesired symptoms, but is generally insufficient
to cause adverse side effects. The specific therapeutically
effective dose level for any particular patient will depend upon a
variety of factors including the disorder being treated and the
severity of the disorder; the specific compounded composition
employed; the age, body weight, general health, sex and diet of the
patient; the time of administration; the route of administration;
the rate of excretion of the specific compounded composition
employed; the duration of the treatment; drugs used in combination
or coincidental with the specific compounded composition employed
and like factors well known in the medical arts. For example, it is
well within the skill of the art to start doses of a compounded
composition at levels lower than those required to achieve the
desired therapeutic effect and to gradually increase the dosage
until the desired effect is achieved. If desired, then the
effective daily dose can be divided into multiple doses for
purposes of administration. Consequently, single dose compounded
compositions can contain such amounts or submultiples thereof to
make up the daily dose. The dosage can be adjusted by the
individual physician in the event of any contraindications. Dosage
can vary, and can be administered in one or more dose
administrations daily, for one or several days. Guidance can be
found in the literature for appropriate dosages for given classes
of pharmaceutical products. In further various aspects, a
preparation can be administered in a "prophylactically effective
amount"; that is, an amount effective for prevention of a disease
or condition, such as, for example, a bacterial infection or a
fungal infection.
[0043] Disclosed are the components to be used to prepare a
disclosed compounded compositions as well as the disclosed
compounded compositions to be used within the methods disclosed
herein. These and other materials are disclosed herein, and it is
understood that when combinations, subsets, interactions, groups,
etc. of these materials are disclosed that while specific reference
of each various individual and collective combinations and
permutation of these compounds cannot be explicitly disclosed, each
is specifically contemplated and described herein. For example, if
a particular compound is disclosed and discussed and a number of
modifications that can be made to a number of molecules including
the compounds are discussed, specifically contemplated is each and
every combination and permutation of the compound and the
modifications that are possible unless specifically indicated to
the contrary. Thus, if a class of molecules A, B, and C are
disclosed as well as a class of molecules D, E, and F and an
example of a combination molecule, A-D is disclosed, then even if
each is not individually recited each is individually and
collectively contemplated meaning combinations, A-E, A-F, B-D, B-E,
B-F, C-D, C-E, and C-F are considered disclosed. Likewise, any
subset or combination of these is also disclosed. Thus, for
example, the sub-group of A-E, B-F, and C-E would be considered
disclosed. This concept applies to all aspects of this application
including, but not limited to, steps in methods of making and using
the compositions of the invention. Thus, if there are a variety of
additional steps that can be performed it is understood that each
of these additional steps can be performed with any specific
embodiment or combination of embodiments of the methods of the
invention.
B. Anti-Infective Agents
[0044] As used herein, an anti-infective agent can be an
antibacterial agent, an antifungal agent, a combination of
antibacterial agents, a combination of antifungal agents, or a
combination of antibacterial agents and antifungal agents.
[0045] Antibacterial agents are known to the art. For example, the
art generally recognizes several categories of antibacterial agents
including (1) enicillins, (2) cephalosporins, (3) fluoroquinolones,
(4) aminoglycosides, (5) monobactams, (6) carbapenems, (7)
macrolides, and (8) other agents. For example, as used herein, an
antibacterial agent can comprise afenide, amikacin, amoxicillin,
ampicillin, arsphenamine, azithromycin, azlocillin, aztreonam,
bacampicillin, bacitracin, carbacephem (loracarbef), carbenicillin,
cefaclor, cefadroxil, cefalotin, cefamandole, cefazolin, cefdinir,
cefditoren, cefepime, cefixime, cefoperazone, cefotaxime,
cefoxitin, cefpodoxime, cefprozil, ceftazidime, ceftibuten,
ceftizoxime, ceftobiprole, ceftriaxone, cefuroxime, cephalexin,
chloramphenicol, chlorhexidine, ciprofloxacin, clarithromycin,
clavulanic acid, clindamycin, cloxacillin, colimycin,
colistimethate teicoplanin, colistin, demeclocycline,
dicloxacillin, dirithromycin, doripenem, doxycycline, efprozil,
enoxacin, ertapenem, erythromycin, ethambutol, flucloxacillin,
fosfomycin, furazolidone, gatifloxacin, geldanamycin, gentamicin,
grepafloxacin, herbimycin, imipenem, isoniazid, kanamycin,
levofloxacin, lincomycin, linezolid, lomefloxacin, meropenem,
meticillin, metronidazole, mezlocillin, minocycline, mitomycin,
moxifloxacin, mupirocin, nafcillin, neomycin, netilmicin,
nitrofurantoin, norfloxacin, ofloxacin, oxacillin, oxytetracycline,
paromomycin, penicillin G, penicillin V, piperacillin
(piperacillin/tazobactam), pivmecillinam, platensimycin, polymyxin
B, prontosil, pvampicillin, pyrazinamide,
quinupristin/dalfopristin, rifampicin, rifampin, roxithromycin,
sparfloxacin, spectinomycin, spiramycin, streptomycin, sulbactam,
sulfacetamide, sulfamethizole, sulfamethoxazole, sulfanilimide,
sulfisoxazole, sulphonamides, sultamicillin, telithromycin,
tetracycline, thiamphenicol, ticarcillin, tobramycin, trimethoprim,
trimethoprim-sulfamethoxazole, troleandomycin, trovafloxacin, or
pharmaceutically acceptable salts thereof, or a combination thereof
In an aspect, fluoroquinolones can comprise enoxacin,
ciprofloxacin, norfloxacin, ofloxacin, levofloxacin, trovafloxacin,
gatifloxacin, and moxifloxacin.
[0046] Antifungal agents may include (1) azoles (imidazoles), (2)
antimetabolites, (3) allylamines, (4) morpholine, (5) glucan
synthesis inhibitors (echinocandins), (6) polyenes, (7)
benoxaaborale; (8) other antifungal/onychomycosis agents, and (9)
new classes of antifungal/onychomycosis agents. For example, as
used herein, an antifungal agent can comprise abafungin,
albaconazole, amorolfin, amphotericin b, anidulafungin, bifonazole,
butenafine, butoconazole, candicidin, caspofungin, ciclopirox,
clotrimazole, econazole, fenticonazole, filipin, fluconazole,
flucytosine, griseofulvin, haloprogin, hamycin, isavuconazole,
isoconazole, itraconazole, ketoconazole, micafungin, miconazole,
naftifine, natamycin, nystatin, omoconazole, oxiconazole,
polygodial, posaconazole, ravuconazole, rimocidin, sertaconazole,
sulconazole, terbinafine, terconazole, tioconazole, tolnaftate,
undecylenic acid, voriconazole, or pharmaceutically acceptable
salts thereof, or a combination thereof In an aspect, azoles can
comprise clotrimazole, econazole, oxiconazole, ketoconazole,
miconazole, sulconazole, fluconazole, itraconazole, and
voriconazole.
[0047] In an aspect, an antifungal agent or antibacterial agent can
comprise an ointment or can comprise a dry powder. In an aspect,
the dry powder can be obtained from crushed tablets comprising an
antifungal agent or from a container comprising the antifungal
agent as a dry powder. In an aspect, an antifungal agent can be
pure or substantially pure and can be obtained from a bulk source.
In an aspect, an antifungal agent can be commercially available as,
for example, a tablet, a cream, an ointment, or a powder.
[0048] As used herein, the recitation of any anti-infective agent
inherently encompasses the pharmaceutically acceptable salts
thereof.
C. Compounded Compositions
[0049] Disclosed herein are compounded compositions for treating an
infection.
1. A First Antibacterial Agent and a Second Anti-Infective
Agent
[0050] Disclosed herein is a compounded composition comprising a
therapeutically effective amount of a first antibacterial agent and
a therapeutically effective amount of a second antibacterial agent.
A disclosed compounded composition can comprise a dry powder
formulation or can comprise an ointment.
[0051] In an aspect, a disclosed compounded composition can
comprise from about 1.0% w/w to about 9.0% w/w, from about 2.0% w/w
to about 8.0% w/w, from about 3.0% w/w to about 7.0% w/w, or from
about 4.0% w/w to about 7.0% w/w of the first antibacterial agent.
In an aspect, a disclosed compounded composition can comprise from
about 1.0% w/w to about 9.0% w/w, from about 2.0% w/w to about 8.0%
w/w, from about 3.0% w/w to about 7.0% w/w, or from about 4.0% w/w
to about 7.0% w/w of the second antibacterial agent.
[0052] The first antibacterial agent may include one or more
antibacterials or pharmaceutically acceptable salts thereof
selected from afenide, amikacin, amoxicillin, ampicillin,
arsphenamine, azithromycin, azlocillin, aztreonam, bacampicillin,
bacitracin, carbacephem (loracarbef), carbenicillin, cefaclor,
cefadroxil, cefalotin, cefamandole, cefazolin, cefdinir,
cefditoren, cefepime, cefixime, cefoperazone, cefotaxime,
cefoxitin, cefpodoxime, cefprozil, ceftazidime, ceftibuten,
ceftizoxime, ceftobiprole, ceftriaxone, cefuroxime, cephalexin,
chloramphenicol, chlorhexidine, ciprofloxacin, clarithromycin,
clavulanic acid, clindamycin, cloxacillin, colimycin,
colistimethate teicoplanin, colistin, demeclocycline,
dicloxacillin, dirithromycin, doripenem, doxycycline, efprozil,
enoxacin, ertapenem, erythromycin, ethambutol, flucloxacillin,
fosfomycin, furazolidone, gatifloxacin, geldanamycin, gentamicin,
grepafloxacin, herbimycin, imipenem, isoniazid, kanamycin,
levofloxacin, lincomycin, linezolid, lomefloxacin, meropenem,
meticillin, metronidazole, mezlocillin, minocycline, mitomycin,
moxifloxacin, mupirocin, nafcillin, neomycin, netilmicin,
nitrofurantoin, norfloxacin, ofloxacin, oxacillin, oxytetracycline,
paromomycin, penicillin G, penicillin V, piperacillin
(piperacillin/tazobactam), pivmecillinam, platensimycin, polymyxin
B, prontosil, pvampicillin, pyrazinamide,
quinupristin/dalfopristin, rifampicin, rifampin, roxithromycin,
sparfloxacin, spectinomycin, spiramycin, streptomycin, sulbactam,
sulfacetamide, sulfamethizole, sulfamethoxazole, sulfanilimide,
sulfisoxazole, sulphonamides, sultamicillin, telithromycin,
tetracycline, thiamphenicol, ticarcillin, tobramycin, trimethoprim,
trimethoprim-sulfamethoxazole, troleandomycin, trovafloxacin, or
pharmaceutically acceptable salts thereof, or a combination
thereof. In an aspect, fluoroquinolones can comprise enoxacin,
ciprofloxacin, norfloxacin, ofloxacin, levofloxacin, trovafloxacin,
gatifloxacin, or moxifloxacin, as discussed supra.
[0053] In an aspect, the first antibacterial agent can comprise
mupirocin. Disclosed herein is a compounded composition comprising
a therapeutically effective amount of mupirocin and a
therapeutically effective amount of a second antibacterial agent.
In an aspect, a disclosed compounded composition comprising
mupirocin and a second antibacterial agent can comprise a dry
powder formulation or can comprise an ointment.
[0054] In an aspect, a disclosed compounded composition comprising
mupirocin and an antibacterial agent can comprise from about 1.0%
w/w to about 3.0% w/w mupirocin. In an aspect, a disclosed
compounded composition comprising mupirocin and an antibacterial
agent can comprise about 1.6% w/w, or about 1.7% w/w, or about 1.8%
w/w mupirocin. In an aspect, a disclosed compounded composition
comprising mupirocin and an antibacterial agent can comprise from
about 1.0% w/w to about 9.0% w/w, from about 2.0% w/w to about 8.0%
w/w, from about 3.0% w/w to about 7.0% w/w, from about 4.0% w/w to
about 6.0% w/w, or about 5.0% w/w of the antibacterial agent. In an
aspect, a disclosed compounded composition comprising mupirocin and
an antibacterial agent can comprise about 2.5% w/w, about 5.0% w/w,
about 6.0%, or about 7.5% w/w of the antibacterial agent (which is
in addition to the amount of mupirocin). Greater or lesser amounts
of mupirocin may be used, e.g., less than about 4%, about 3%, about
2%, or about 1% mupirocin.
[0055] In an aspect, the first antibacterial agent comprises a
therapeutically effective amount of streptomycin. In some
embodiments, the compounded composition comprises a therapeutically
effective amount of streptomycin and a therapeutically effective
amount of a second antibacterial agent. In an aspect, a disclosed
compounded composition comprising streptomycin alone or in
combination with a second antibacterial agent comprises a dry
powder formulation or ointment. As described in more detail below,
the dry powder or ointment may be further compounded with a
diluent, which may also be a carrier, to formulate a compounded
composition comprising a cream, ointment, emulsion (o/w, w/o), gel,
jelly, wax, solution. The compounded composition may be formulated
for topical administration for local or systemic action. In various
embodiments, the compounded composition comprises a topical
composition for otic, nasal, upper or lower respiratory tract
administration.
[0056] The second antibacterial agent may include one or more
antibacterials or pharmaceutically acceptable salts thereof
selected from afenide, amikacin, amoxicillin, ampicillin,
arsphenamine, azithromycin, azlocillin, aztreonam, bacampicillin,
bacitracin, carbacephem (loracarbef), carbenicillin, cefaclor,
cefadroxil, cefalotin, cefamandole, cefazolin, cefdinir,
cefditoren, cefepime, cefixime, cefoperazone, cefotaxime,
cefoxitin, cefpodoxime, cefprozil, ceftazidime, ceftibuten,
ceftizoxime, ceftobiprole, ceftriaxone, cefuroxime, cephalexin,
chloramphenicol, chlorhexidine, ciprofloxacin, clarithromycin,
clavulanic acid, clindamycin, cloxacillin, colimycin,
colistimethate teicoplanin, colistin, demeclocycline,
dicloxacillin, dirithromycin, doripenem, doxycycline, efprozil,
enoxacin, ertapenem, erythromycin, ethambutol, flucloxacillin,
fosfomycin, furazolidone, gatifloxacin, geldanamycin, gentamicin,
grepafloxacin, herbimycin, imipenem, isoniazid, kanamycin,
levofloxacin, lincomycin, linezolid, lomefloxacin, meropenem,
meticillin, metronidazole, mezlocillin, minocycline, mitomycin,
moxifloxacin, mupirocin, nafcillin, neomycin, netilmicin,
nitrofurantoin, norfloxacin, ofloxacin, oxacillin, oxytetracycline,
paromomycin, penicillin G, penicillin V, piperacillin
(piperacillin/tazobactam), pivmecillinam, platensimycin, polymyxin
B, prontosil, pvampicillin, pyrazinamide,
quinupristin/dalfopristin, rifampicin, rifampin, roxithromycin,
sparfloxacin, spectinomycin, spiramycin, streptomycin, sulbactam,
sulfacetamide, sulfamethizole, sulfamethoxazole, sulfanilimide,
sulfisoxazole, sulphonamides, sultamicillin, telithromycin,
tetracycline, thiamphenicol, ticarcillin, tobramycin, trimethoprim,
trimethoprim-sulfamethoxazole, troleandomycin, trovafloxacin, or
pharmaceutically acceptable salts thereof, or a combination
thereof. In an aspect, fluoroquinolones can comprise enoxacin,
ciprofloxacin, norfloxacin, ofloxacin, levofloxacin, trovafloxacin,
gatifloxacin, or moxifloxacin, as discussed supra.
[0057] In an aspect, a disclosed compounded composition comprising
streptomycin and a second antibacterial agent comprises from about
1.0% w/w to about 10.0% w/w streptomycin. In an aspect, a disclosed
compounded composition comprising streptomycin and a second
antibacterial agent comprises about 3% w/w, or about 6% w/w, or
about 8% w/w streptomycin. In an aspect, a disclosed compounded
composition comprising streptomycin and a second antibacterial
agent comprises from about 1.0% w/w to about 9.0% w/w, from about
2.0% w/w to about 8.0% w/w, from about 3.0% w/w to about 7.0% w/w,
from about 4.0% w/w to about 6.0% w/w, or about 5.0% w/w of the
second antibacterial agent. Greater or lesser amounts of
streptomycin or second antibacterial agent may be used, e.g., less
than about 1.5%, about 1%, about 0.5%, or about 0.25% second
antibacterial agent by weight. In various embodiments, the
compounded composition comprising a dry powder, topical solution,
or other compounded topical formulation includes an amount of
streptomycin configured to provide less than or equal to 1 gm of
delivered streptomycin per day, such as less than about 25 mg,
about 50 mg, about 75 mg, about 100 mg, about 200 mg, about 300 mg,
about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800
mg, or about 900 mg. For example, the strength of a compounded
composition for topical administration with respect to streptomycin
may be determined by the amount of streptomycin that may be
delivered using the desired format and number of treatments per
day. Accordingly, the compounded composition may be formulated such
that it may be contacted with a body surface of a subject that is
infected or suspected to be infected with a suitable amount of the
compounded composition to topically deliver between 25 mg and 1 gm
of streptomycin per day, such as between about 25 mg and about 900
mg, about 25 mg and about 500 mg, about 25 mg and about 200 mg,
about 50 mg and about 1 gm, about 50 mg and about 800 mg, about 50
mg and about 500 mg, about 50 mg and about 200 mg, about 100 mg and
about 1 gm, about 100 mg and about 800 mg, about 100 mg and about
500 mg, about 300 mg and about 1 gm, about 300 mg and about 800 mg,
about 300 mg and about 500 mg. about 500 mg and about 1 gm, about
500 mg and about 800 mg, or about 800 mg and about 1 gm. The ratio
of second anti-infective agent, when present, to streptomycin in a
compounded composition, which may include compounded capsules,
compounded ointments, compounded topical compositions obtained by
mixing a compounded composition, such as a compounded capsule or
compounded ointment, with a diluent at the time of administration,
may be 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, about 1:10, about 1:12, about
1:14, about 1:15, about 1:20, or less. In various embodiments, the
ratio of the second anti-infective agent to the first
anti-infective agent is between about 1:1 and 1:20, 1:2 and about
1:15, about 1:3 and about 1:15, about 1:3 and about 1:10, about 1:4
and about 1:15, or about 1:4 and about 1:10.
[0058] In an aspect, the second antibacterial agent can comprise
colistimethate. The colistimethate may be compounded from a dry
powder such as colistimethate for injection. In an aspect, the
second antibacterial agent comprises tobramycin or a
pharmaceutically acceptable salt thereof. The tobramycin may be
compounded as tobramycin sulfate. In an aspect, the second
antibacterial agent can comprise doxycycline or a pharmaceutically
acceptable salt thereof. In an aspect, the second antibacterial
agent can comprise doxycycline hyclate. In an aspect, the second
antibacterial agent can comprise azithromycin. In an aspect, the
first antibacterial agent can comprise mupirocin and the second
antibacterial agent can comprise one or more of bacitracin,
colistimethate, piperacillin-tazobactam, polymyxin B, streptomycin
or pharmaceutically acceptable salts thereof In an aspect, the
first antibacterial agent comprises mupirocin and the second
antibacterial agent comprises an antibacterial selected from
colistimethate, clindamycin, levofloxacin, streptomycin, or
combination thereof. In an aspect, the first antibacterial agent
comprises streptomycin and the second antibacterial agent comprises
an antibacterial selected from colistimethate, clindamycin,
levofloxacin, mupirocin, or combination thereof. One or both of the
first antibacterial agent or the second antibacterial agent may
comprise dry powder for injection. In one example, the streptomycin
comprises streptomycin for injection USP. In a further example, the
streptomycin comprises streptomycin sulfate for injection USP. In
one example, the mupirocin comprises a dry powder, such as a bulk
powder. The mupirocin can comprise an ointment (for example, a
mupirocin 2.0% ointment) and the second antibacterial agent may
comprise a dry powder. In one embodiment, the second antibacterial
agent comprises bacitracin. In one example, the bacitracin
comprises bacitracin for injection (USP). In another embodiment,
the second antibacterial agent comprises colistimethate. In one
example, the colistimethate comprises colistimethate for injection.
In a further example, the colistimethate includes colistimethate
for injection comprising colistimethate sodium or pentasodium
colistin methanesulfonate. In another embodiment, the second
antibacterial agent comprises piperacillin-tazobactam. In one
example, the piperacillin-tazobactam comprises
piperacillin-tazobactam for injection USP. In a further example,
the piperacillin-tazobactam comprises piperacillin-tazobactam for
injection USP selected from 2.25 gram, 3.375 gram, and 4.5 gram
vials. In another embodiment, the second antibacterial agent
comprises polymyxin B. In one example, the polymyxin B comprises
Polymyxin B for Injection USP. In another embodiment, the second
antibacterial agent comprises streptomycin.
[0059] In various embodiments, the second anti-infective agent
comprises an antifungal agent comprising one or more antifungals
pharmaceutically acceptable salts thereof selected from abafungin,
albaconazole, amorolfin, amphotericin b, anidulafungin, bifonazole,
butenafine, butoconazole, candicidin, caspofungin, ciclopirox,
clotrimazole, econazole, fenticonazole, filipin, fluconazole,
flucytosine, griseofulvin, haloprogin, hamycin, isavuconazole,
isoconazole, itraconazole, ketoconazole, micafungin, miconazole,
naftifine, natamycin, nystatin, omoconazole, oxiconazole,
polygodial, posaconazole, ravuconazole, rimocidin, sertaconazole,
sulconazole, terbinafine, terconazole, tioconazole, tolnaftate,
undecylenic acid, voriconazole, or pharmaceutically acceptable
salts thereof, or a combination thereof In an aspect, azoles can
comprise clotrimazole, econazole, oxiconazole, ketoconazole,
miconazole, sulconazole, fluconazole, itraconazole, or
voriconazole, as discussed supra. The antifungal agent may be in
addition to or instead of the second antibacterial agent.
[0060] In one embodiment, a compounded composition comprises a
therapeutically effective amount of mupirocin, streptomycin, or
both and a therapeutically effective amount of an antifungal agent.
A disclosed compounded composition comprising mupirocin,
streptomycin, or both and the antifungal agent can comprise a dry
powder formulation or can comprise an ointment. As described in
more detail elsewhere in the present disclosure, the dry powder or
ointment may be further compounded with a carrier or diluent to
formulate a compounded composition comprising a cream, ointment,
emulsion (o/w, w/o), gel, jelly, wax, solution. The compounded
composition may be formulated for topical administration for local
or systemic action. In various embodiments, the compounded
composition comprises a topical composition for otic, nasal, upper
or lower respiratory tract administration.
[0061] The antifungal agent may comprise one or more antifungals
selected from abafungin, albaconazole, amorolfin, amphotericin b,
anidulafungin, bifonazole, butenafine, butoconazole, candicidin,
caspofungin, ciclopirox, clotrimazole, econazole, fenticonazole,
filipin, fluconazole, flucytosine, griseofulvin, haloprogin,
hamycin, isavuconazole, isoconazole, itraconazole, ketoconazole,
micafungin, miconazole, naftifine, natamycin, nystatin,
omoconazole, oxiconazole, polygodial, posaconazole, ravuconazole,
rimocidin, sertaconazole, sulconazole, terbinafine, terconazole,
tioconazole, tolnaftate, undecylenic acid, voriconazole, or
pharmaceutically acceptable salts thereof, or a combination thereof
In an aspect, azoles can comprise clotrimazole, econazole,
oxiconazole, ketoconazole, miconazole, sulconazole, fluconazole,
itraconazole, or voriconazole, as discussed supra. The antifungal
agent may be in addition to or instead of the second antibacterial
agent.
[0062] In an aspect, a disclosed compounded composition comprising
streptomycin and an antifungal agent comprises from about 1.0% w/w
to about 10.0% w/w streptomycin. In an aspect, a disclosed
compounded composition comprising streptomycin and an antifungal
agent comprises about 3% w/w, or about 6% w/w, or about 8% w/w
streptomycin. In an aspect, a disclosed compounded composition
comprising streptomycin and an antifungal agent comprises from
about 1.0% w/w to about 9.0% w/w, from about 2.0% w/w to about 8.0%
w/w, from about 3.0% w/w to about 7.0% w/w, from about 4.0% w/w to
about 6.0% w/w, or about 5.0% w/w of the antifungal agent. Greater
or lesser amounts of streptomycin or second antibacterial agent may
be used, e.g., less than about 1.5%, about 1%, about 0.5%, or about
0.25% antifungal agent by weight.
[0063] In an aspect, a disclosed compounded composition can
comprise a therapeutically effective amount of one or more
additional anti-infective agents. In an aspect, the additional
anti-infective agent can be an antibacterial agent. Antibacterial
agents are known to the art and discussed supra. In an aspect, the
additional anti-infective agent can be an antifungal agent. In an
aspect, the antifungal agent can comprise ketoconazole.
[0064] In an aspect, a disclosed compounded composition can
comprise one or more excipients or additives. In an aspect,
excipients or additives include, but are not limited to, the
following: solvents, surfactants, humectants, preservatives,
flavorings, stabilizers (including antioxidants), binders, and
colorants.
[0065] Disclosed herein is a compounded composition comprising a
therapeutically effective amount of an anti-infective comprising at
least streptomycin. The streptomycin may comprise a dry powder,
such as a powder for injection.
[0066] The compounded composition may include multiple
anti-infectives in combination with streptomycin, such as
streptomycin for injection. The multiple anti-infectives may be
selected from any combination of the antibacterial and antifungals
described herein. In one example, one or more of the
anti-infectives may comprise one or more antibacterials or
pharmaceutically acceptable salt thereof selected from bacitracin,
colistimethate, piperacillin-tazobactam, polymyxin B, streptomycin,
or combination thereof and/or one or more one or more antifungals
or pharmaceutically acceptable salt thereof selected from
voriconazole, amphotericin B, or combination thereof. In these or
other embodiments, one or more of the anti-infectives may comprise
the antibacterial doxycycline or pharmaceutically acceptable salt
and/or the antifungal ketoconazole or pharmaceutically acceptable
salt thereof. In some embodiments, streptomycin alone or in
combination with one or more additional anti-infectives may be
compounded in an ointment. In various embodiments, the compounded
composition comprising a compounded ointment may include about 20%
or less streptomycin by weight. In some examples, the compounded
ointment may include from about 1% to about 15%, about 1% to about
10%, about 1% to about 5%, about 5% to about 10% streptomycin by
weight.
[0067] In various embodiments, the compounded composition comprises
a dry powder formulation, ointment, or combination thereof
comprising streptomycin alone or in combination with another
anti-infective as described herein and may be formulated for direct
administration or mixing with a diluent, which may also be or
comprise a carrier. For example, a dry powder formulation may be
utilized as an inhalable powder or wound powder, which may be
administered directly. In some embodiments, the diluent may
comprise a liquid, e.g., an aqueous or organic diluent, a dry
powder diluent, a topical cream, lotion, ointment, emulsion (o/w,
w/o), gel, wax, or jelly. For example, a dry powder formulation may
be mixed with a diluent comprising a dry powder diluent wherein the
resulting mixture may be administered as an inhalable powder or
wound powder. In various embodiments, a dry powder formulation may
be formulated to be mixed with a diluent at the time of
administration to produce a mixture comprising the compounded
composition having about 20% or less streptomycin by weight. In
some examples, the mixture comprising the compounded composition
may include from about 1% to about 15%, about 1% to about 10%,
about 1% to about 5%, about 5% to about 10% streptomycin by
weight.
[0068] In one example, the compounded composition a dry powder
formulation or compounded ointment is formulated for mixing with a
liquid diluent just prior to administration. In various
embodiments, for example, a resulting mixture comprises a topical
composition for irrigation, e.g., wound irrigation to treat broken
tissue or administration to infected skin in a foot bath. In some
embodiments, the resulting mixture comprises a topical solution for
nasal administration or administration to the upper or lower
respiratory tract, e.g., in a nasal spray, mist, drop, irrigation,
nebulization formulation. In some embodiments, the resulting
mixture comprises a topical solution for otic administration or
administration to the upper or lower respiratory tract, e.g., in a
nasal spray, mist, drop, irrigation, or nebulization
formulation.
[0069] In another example, the compounded composition is formulated
for mixing with a dry powder diluent such as lactose for
administration by inhalation. In another example, the compounded
composition is formulated for mixing with a dry powder diluent for
administration to a wound comprising broken tissue, such as a wet
wound whereby the resulting dry powder mixture contacts the wet
wound and at least partially solubilizes thereon.
[0070] In another example, the compounded composition is formulated
for mixing with a topical cream, lotion, ointment, gel, emulsion
(o/w, w/o), wax, or jelly. The resulting mixture may be applied to
skin or other body surface for topical administration. In one
example, the resulting mixture may be applied to a medical
instrument for application to skin or a body surface, such as a
body orifice, or for providing a barrier between the instrument and
the skin or body surface during a procedure. In one example, the
compounded composition comprises a dry powder of one or more
antibacterial agents formulated to be mixed with an anti-infective
comprising an ointment such as a commercially available mupirocin
ointment.
[0071] In some embodiments, a compounded composition may include a
compounded ointment comprising streptomycin. The compounded
ointment may be compounded from a dry powder streptomycin, e.g.,
streptomycin for injection such as streptomycin sulfate for
injection. The compounded composition comprising a compounded
ointment may include about 20% or less streptomycin by weight. In
some examples, the compounded ointment may include from about 1% to
about 15%, about 1% to about 10%, about 1% to about 5%, about 5% to
about 10% streptomycin by weight. In various embodiments, the
compounded ointment may include between about 1% and about 10%
streptomycin by weight. The compounded ointment may be further
compounded with the second antibacterial agent comprising a dry
powder or ointment, which may be applied directly to infected skin
or may be further combined with an aqueous diluent for irrigation
administration, e.g., in a foot bath. In some embodiments, the dry
powder formulation comprising streptomycin alone or in combination
with one or more second anti-infectives may be applied directly to
infected skin. For example, a dry powder formulation comprising
streptomycin alone or in combination with one or more additional
anti-infectives may be applied to infected and/or broken tissues,
such as a wet wound. In some embodiments, the dry powder
formulation comprising streptomycin alone or in combination with
one or more second anti-infectives may be mixed with a suitable
diluent as described above and elsewhere herein. In one embodiment,
a dry powder formulation comprising streptomycin alone or in
combination with one or more additional anti-infectives may be
compounded with an ointment comprising an additional
anti-infective. For example, a dry powder formulation comprising
streptomycin alone or in combination with one or more additional
anti-infectives may be mixed with a mupirocin ointment to form a
compounded ointment. In an aspect a disclosed composition comprises
an ointment comprising a therapeutic amount of streptomycin. In one
example, the ointment comprises streptomycin in an amount between
about 1% and about 10% by weight. In a further embodiment, the
ointment may comprise an additional anti-infective such as one or
more antibacterial or antifungal agents as described herein. For
example, the second anti-infective may comprise an antibacterial
selected from colistimethate, clindamycin, mupirocin, levofloxacin,
or combination thereof.
[0072] As introduced above, the compounded composition may include
additional anti-infectives, such as a second antibacterial agent
and an antifungal agent may comprise powders.
[0073] In an aspect, the compounded composition may include an
amount of second antibacterial agent from about 1% to about 30%,
about 1% to about 20%, about 1% to about 10%, about 1% to about 5%,
about 4% to about 15%, about 4% to about 10%, or about 4% to about
8% w/w. In an aspect, the compounded composition may include an
amount of antifungal agent from about 1% to about 30%, about 1% to
about 20%, about 1% to about 10%, about 1% to about 5%, about 2% to
about 15%, about 2% to about 10%, or about 2% to about 8% w/w. In
various embodiments, the powders may comprise anti-infective
tablets (ground, e.g., crushed), bulk powder, or anti-infective for
injection. Anti-infectives for injection may comprise powder,
typically available in vials, for reconstitution.
[0074] In some embodiments, the compounded composition may include
from about 1% to about 30%, about 1% to about 20%, about 4% to
about 20%, about 4% to about 15% w/w anti-infective for injection.
In various embodiments, the compounded composition comprises
anti-infective for injection in an amount between about 3% and
about 20% w/w. In an aspect, the anti-infective for injection
comprises streptomycin sulfate for injection. In an aspect, the
anti-infectective for injection comprises streptomycin sulfate for
injection and one or more of bacitracin for injection,
colistimethate sodium for injection, pentasodium colistin
methanesulfonate for injection, piperacillin-tazobactam for
injection, polymyxin B for injection USP, tobramycin sulfate for
injection, voriconazole for injection, or amphotericin B for
injection. In these or other embodiments, the compounded
composition may include from about 1% to about 30%, about 1% to
about 20%, about 1% to about 10%, about 3% to about 15%, or about
4% to about 12% crushed anti-infective tablets.
[0075] In various embodiments, the compounded composition comprises
a sufficient amount of an excipient base powder comprising a blend
of micronized xylitol and poloxamers, and a sufficient amount of
xylitol. In an aspect, an excipient base powder comprising a blend
a micronized xylitol and poloxamers can be LoxaSperse.TM. excipient
base powder. In an aspect, an excipient base powder comprising a
blend a micronized xylitol and poloxamers can be XyliFos.TM.
excipient base powder. Excipient base powders are known to the art
and discussed supra. In an aspect, a disclosed compounded
composition comprising an excipient base powder and xylitol can
comprise a weight ratio of excipient base powder to xylitol of
about 1:1, about 1:2, about 1:3, about 1:4, about 1:5, about 1:6,
about 1:7, from about 1:1 to about 1:7, from about 1:2 to about
1:6, or from about 1:4 to about 1:5. In an aspect, the weight ratio
of excipient base powder to xylitol can be about 1:4.35.
2. Capsules
[0076] In various embodiments, a container may be provided to
contain the compounded composition. For example, the compounded
composition may be contained in one or more capsules. Capsules may
include dry powder obtained from crushed tablets, bulk powders,
antimicrobials for injection, or combinations thereof.
[0077] In an aspect, a disclosed capsule can comprise about 100 mg
to about 2000 mg of a disclosed compounded composition. In an
aspect, a disclosed capsule can comprise about 100 mg, about 150
mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about
400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg,
about 650 mg, about 700 mg, about 750, about 800 mg, about 850 mg,
about 900 mg, about 950 mg, about 1000 mg, about 1050 mg, about
1100 mg, about 1150 mg, about 1200 mg, about 1250 mg, about 1300
mg, about 1350 mg, about 1400 mg, about 1450 mg, about 1500 mg,
about 1550 mg, about 1600 mg, about 1650 mg, about 1700 mg, about
1750 mg, about 1800 mg, about 1850 mg, about 1900 mg, about 1950
mg, or about 2000 mg of a disclosed compounded composition.
[0078] In an aspect, a disclosed capsule comprising a disclosed
compounded composition can be broken apart such that its contents
can be retrieved. In an aspect, a disclosed capsule can be
dissolved in water such that its contents can be contacted with the
water.
[0079] In an aspect, a disclosed capsule can comprise one or more
additional anti-infective agents. In an aspect, the additional
anti-infective agent can be a dry powder. In an aspect, the
additional anti-infective agent can be an ointment. The additional
anti-infective agent can be pure or substantially pure. The
additional anti-infective agent can be obtained from a bulk source.
In an aspect, the additional anti-infective agent can be an
antibacterial agent. Antibacterial agents are known to the art and
discussed supra. In an aspect, the additional anti-infective agent
can be an antifungal agent. Antifungal agents are known to the art
and discussed supra.
[0080] In one embodiment, a compounded capsule comprises between
about 25 mg and about 500 mg streptomycin with streptomycin being
the primary ingredient in the capsule. In some embodiments, the
compounded capsule includes a second anti-infective comprising one
or more anti-infectives, such as antibacterials and/or antifungals
described herein. For example, the second anti-infective may
comprise an antibacterial selected from colistimethate,
clindamycin, mupirocin, levofloxacin, or combination thereof.
[0081] In an aspect, a compounded capsule may include between about
50 mg and about 250 mg streptomycin. In some embodiments, the
compounded capsule may include a second anti-infective agent
comprising one or more additional anti-infectives comprising an
antibacterial, antifungal, or combination thereof. The second
anti-infective may be present in an amount less than or greater
than the streptomycin. In various embodiments, the second
anti-infective agent may be present in lesser amount than the
streptomycin. For example, the second anti-infective agent may be
present in an amount less than about 100 mg, less than about 75 mg,
less than about 50 mg, or less than about 25 mg. In various
embodiments, a compounded capsule may include a second
anti-infective agent comprising an antibacterial selected from
colistimethate, clindamycin, mupirocin, levofloxacin, or
combination thereof. In some embodiments, the second anti-infective
agent may be present in an amount between about 25 mg and about 100
mg, about 25 mg and about 25 mg, about 25 mg and about 50 mg, or
about 50 mg and about 75 mg. For example, in one embodiment, a
compounded capsule includes between about 50 mg and about 225 mg
streptomycin and between about 25 and about 75 mg colistimethate.
In another example, a compounded capsule includes between about 50
mg and about 225 mg streptomycin and between about 25 mg and about
50 mg mupirocin.
[0082] In various embodiments, the anti-infectives may be obtained
from bulk powder, crushed tablets, or injectable powders as
described herein. In an aspect, a disclosed capsule or the contents
thereof may be combined with a carrier or diluent to formulate a
compounded composition comprising a powder, cream, ointment,
emulsion (o/w, w/o), gel, jelly, wax, solution. A compounded
ointment, for example, may include an antibacterial agent
comprising between about 1% and about 10% streptomycin by weight.
The compounded ointment may also include one or more additional
anti-infectives. The additional anti-infective, when included, may
be present in an amount less than or greater than the streptomycin,
such as less or greater than about 10%, less than about 5%, less
than about 3%, less than about 1% by weight.
[0083] In an aspect, a disclosed capsule can comprise one or more
excipients or additives. In an aspect, excipients or additives
include, but are not limited to, the following: solvents,
surfactants, humectants, preservatives, flavorings, stabilizers
(including antioxidants), binders, and colorants.
3. Kits
[0084] Disclosed herein is a kit, comprising: a plurality of
containers, each container comprising a compounded composition.
[0085] In an aspect, the plurality of containers can comprise more
than 1 container. In an aspect, the plurality can comprise at least
3 containers, at least 7 containers, or at least 10 containers, at
least 14 containers, at least 21 containers, at least 30
containers, at least 60 containers, at least 90 containers, at
least 120 containers, or at least 150 containers, or more than 150
containers.
[0086] In an aspect, the plurality of containers can comprise a 3
day's supply, or a week's supply, or a 10 day's supply, or a two
week's supply, or a month's supply, or a two month's supply, or a
three month's supply, or a six month's supply, or more than a six
month's supply of a disclosed compounded composition.
[0087] It will be appreciated that the compound composition may be
provided in containers other than a capsule. For example, the
compounded composition may be provided in a pouch, vial, or other
suitable container. For example, a kit may comprise one or more
capsules containing a therapeutically effective of amount of one or
more anti-infectives as described herein, such as mupirocin or
streptomycin, in a dry powder formulation or ointment, and a
diluent, which may comprise a carrier. The diluent may comprise a
dry powder, cream, ointment, emulsion (o/w, w/o), gel, jelly, wax,
solution. Solutions may include, for example, water (e.g., potable
water, sterile water, water for injection), aqueous based
solutions, oil based solutions, organic solvents, saline (e.g.,
0.9% saline, normal saline), povidone iodine, sodium hypochlorite
(Dakin's solution), hydrogen peroxide, cleansers (e.g., wound
cleansers). Such solutions may be sterile solutions. Prior to,
e.g., at the time of administration, of the compounded composition,
the contents of the capsule may be mixed with the carrier or
diluent.
[0088] In some embodiments, a kit comprising the compounded
composition is provided compounded in the diluent. For example, the
compounded composition may comprise a cream, ointment, emulsion
(o/w, w/o), gel, jelly, wax, solution comprising one or more
anti-infectives as described herein. In one example, a kit
comprises a compounded composition in the form of a compounded
ointment and that may be further mixed with a diluent prior to
administration, e.g., for administration in a foot bath, irrigation
format, or otherwise. In various embodiments, a kit includes a
compounded composition comprising a dry powder. The dry powder may
be provided in one or more containers, e.g., one or more compounded
capsules. For example, a kit may include a compounded capsule
comprising between about 50 mg and about 250 mg streptomycin. In
some embodiments, the compounded capsule may include a second
anti-infective agent comprising one or more additional
anti-infectives comprising an antibacterial, antifungal, or
combination thereof. The second anti-infective may be present in an
amount less than or greater than the streptomycin. In various
embodiments, the second anti-infective agent may be present in
lesser amount than the streptomycin. For example, the second
anti-infective agent may be present in an amount less than about
100 mg, less than about 75 mg, less than about 50 mg, or less than
about 25 mg. In various embodiments, a compounded capsule may
include a second anti-infective agent comprising an antibacterial
selected from colistimethate, clindamycin, mupirocin, levofloxacin,
or combination thereof. In some embodiments, the second
anti-infective agent may be present in an amount between about 25
mg and about 100 mg, about 25 mg and about 25 mg, about 25 mg and
about 50 mg, or about 50 mg and about 75 mg. For example, in one
embodiment, a compounded capsule includes between about 50 mg and
about 225 mg streptomycin and between about 25 and about 75 mg
colistimethate. In another example, a compounded capsule includes
between about 50 mg and about 225 mg streptomycin and between about
25 mg and about 50 mg mupirocin.
[0089] In various embodiments, a kit includes one or more
anti-infectives comprising streptomycin alone or in combination
with one or more anti-infectives as described herein. The
streptomycin may be provided as a dry powder, which may be
contained in a container such as a capsule alone or in combination
with one or more additional anti-infectives as described herein. In
one embodiment, the additional anti-infective comprises one or more
anti-infectives selected from colistimethate, clindamycin,
mupirocin, levofloxacin, or combination thereof. One or more
additional anti-infectives may be provided in the kit in another
format, e.g., a solution, ointment, or other suitable format. For
example, a kit may comprise streptomycin powder and mupirocin
ointment, such as mupirocin 2% ointment. The streptomycin powder
may be mixed with the mupirocin ointment prior to administration.
The kit may also include diluents to be mixed with the combination
powder and ointment.
[0090] In various embodiments, a kit comprising a dry powder
formulation of streptomycin alone or in combination with one or
more additional anti-infectives may comprise an inhalable powder or
wound powder formulation configured to be administered directly to
a subject's tissues. In one embodiment, the additional
anti-infective one or more antibacterials selected from
colistimethate, clindamycin, mupirocin, levofloxacin, or
combination thereof. In one example, the kit may provide a
nebulization formulation whereby, at the time of administration,
the dry powder formulation may be mixed with a suitable sterile
liquid diluent for nebulization.
[0091] In an embodiment, a kit comprises a compounded ointment
comprising streptomycin alone or in combination with one or more
additional anti-infectives, such as an antibacterial agent and/or
an antifungal agent. In one example, a kit comprises a compounded
ointment comprising streptomycin in combination with one or more
antibacterials selected from colistimethate, clindamycin,
mupirocin, levofloxacin, or combination thereof. In some
embodiments, the compounded ointment includes from about 1% to
about 15%, about 1% to about 10%, about 1% to about 5%, about 5% to
about 10% streptomycin by weight.
[0092] In various embodiments, a kit comprising a compounded
ointment comprising streptomycin alone or in combination with one
or more additional anti-infectives as described herein may also
include a diluent for mixing with the anti-infectives prior to or
at the time of administration. In one example, one or more
additional anti-infectives may comprise colistimethate,
clindamycin, mupirocin, levofloxacin, or combination thereof. The
diluent may comprise a dry powder, cream, ointment, emulsion (o/w,
w/o), gel, jelly, wax, solution. Solutions may include, for
example, water (e.g., potable water, sterile water, water for
injection), aqueous based solutions, oil based solutions, organic
solvents, saline (e.g., 0.9% saline, normal saline), povidone
iodine, sodium hypochlorite (Dakin's solution), hydrogen peroxide,
cleansers (e.g., wound cleansers). Prior to, e.g., at the time of
administration, of the compounded composition, a suitable amount of
the compounded ointment may be mixed with the carrier or diluent.
As noted above, a kit comprising a dry powder formulation or
ointment including an anti-infective agent such as streptomycin
alone or in combination with one or more additional anti-infective
agents may comprise a diluent for mixing with the dry powder
formulation at the time of administration. In various embodiments,
a dry powder formulation may be formulated to be mixed with a
diluent at the time of administration to produce a mixture
comprising the compounded composition having about 20% or less
streptomycin by weight. In some examples, the mixture comprising
the compounded composition may include from about 1% to about 15%,
about 1% to about 10%, about 1% to about 5%, about 5% to about 10%
streptomycin by weight. In various embodiments, the diluent may
comprise a liquid, e.g., an aqueous or organic diluent, a dry
powder diluent, a topical cream, lotion, ointment, emulsion (o/w,
w/o), gel, wax, or jelly. For example, a dry powder formulation may
be mixed with a diluent comprising a dry powder diluent wherein the
resulting mixture may be administered as an inhalable powder or
wound powder. In one example, the kit comprising the compounded
composition includes a liquid diluent for mixing with the compound
composition at the time of administration. The liquid diluent may
comprise a sterile liquid. In various embodiments, for example, a
resulting mixture comprises a topical composition for irrigation,
e.g., wound irrigation for broken tissue or administration to
infected skin in a foot bath. In some embodiments, the resulting
mixture comprises a topical solution for nasal administration or
administration to the upper or lower respiratory tract, e.g., in a
nasal spray, mist, drop, irrigation, nebulization formulation. In
some embodiments, the resulting mixture comprises a topical
solution for otic administration.
[0093] In another example, a kit comprises a compounded composition
comprising streptomycin alone or in combination with an additional
anti-infective and a dry powder diluent for mixing prior to
administration. For example, the dry powder diluent may comprise
lactose whereby the resulting mixture is formulated for
administration by inhalation. In another example, a kit comprises a
compounded composition comprising streptomycin alone or in
combination with an additional anti-infective and a dry powder
diluent configured for mixing prior to administration to a wound
and/or broken tissue, such as a wet wound, whereby the resulting
dry powder mixture contacts the wet wound and at least partially
solubilizes thereon. In another example, a kit comprises a
compounded composition and a diluent comprising a topical cream,
lotion, ointment, gel, emulsion (o/w, w/o), wax, or jelly for
mixing prior to administration. The resulting mixture may be
applied to skin or other body surface for topical administration.
In one example, the resulting mixture may be applied to a medical
instrument for application to skin or a body surface, such as a
body orifice, or for providing a barrier between the instrument and
the skin or body surface during a procedure. In one example, the
compounded composition comprises a dry powder of one or more
antibacterial agents formulated to be mixed with an anti-infective
comprising an ointment such as a commercially available mupirocin
ointment.
[0094] In various embodiments, the compounded composition
comprising a dry powder, topical solution, or other compounded
topical formulation includes an amount of streptomycin configured
to provide less than or equal to 1 gm of delivered streptomycin per
day, such as less than about 25 mg, about 50 mg, about 75 mg, about
100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg,
about 600 mg, about 700 mg, about 800 mg, or about 900 mg. For
example, the strength of a compounded composition for topical
administration with respect to streptomycin may be determined by
the amount of streptomycin that may be delivered using the desired
format and number of treatments per day. Accordingly, a kit may
include a suitable amount of diluent to formulate the mixed
compounded composition for administration. Thus, according to at
least one embodiment, the compounded composition may be formulated
such that it may be contacted with a body surface of a subject that
is infected or suspected to be infected with a suitable amount of
the compounded composition to topically deliver between 25 mg and 1
gm of streptomycin per day, such as between about 25 mg and about
900 mg, about 25 mg and about 500 mg, about 25 mg and about 200 mg,
about 50 mg and about 1 gm, about 50 mg and about 800 mg, about 50
mg and about 500 mg, about 50 mg and about 200 mg, about 100 mg and
about 1 gm, about 100 mg and about 800 mg, about 100 mg and about
500 mg, about 300 mg and about 1 gm, about 300 mg and about 800 mg,
about 300 mg and about 500 mg. about 500 mg and about 1 gm, about
500 mg and about 800 mg, or about 800 mg and about 1 gm. The ratio
of second anti-infective agent, when present, to streptomycin in a
compounded composition, which may include compounded capsules,
compounded ointments, compounded topical compositions obtained by
mixing a compounded composition, such as a compounded capsule or
compounded ointment, with a diluent at the time of administration,
may be 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, about 1:10, about 1:12, about
1:14, about 1:15, about 1:20, or less. In various embodiments, the
ratio of the second anti-infective agent to the first
anti-infective agent is between about 1:1 and 1:20, 1:2 and about
1:15, about 1:3 and about 1:15, about 1:3 and about 1:10, about 1:4
and about 1:15, or about 1:4 and about 1:10.In an aspect, a
disclosed kit can comprise a foot bath. Foot baths are known to the
art and are discussed supra. In an aspect, a disclosed kit can
comprise one or more funnels. In an aspect, a disclosed kit can
comprise one or more mixing containers. In an aspect, a disclosed
kit can comprise one or more scoops or spoons, such as a 5 cc scoop
or spoon or a 1 cc scoop or spoon. In an aspect, a disclosed kit
can comprise one or more keys. In an aspect, a disclosed kit can
comprise a diluent for a disclosed compounded composition. In an
aspect, a diluent can comprise sodium hypochlorite. In an aspect, a
diluent can comprise Dakin's solution. In an aspect, a disclosed
kit can comprise one or more bottles of diluent.
[0095] In an aspect, a disclosed kit can comprise non-stick,
hypo-allergenic tape, sterile pads, sterile applicators (e.g.,
sterile 6 inch applicators), or a combination thereof In an aspect,
a disclosed kit can comprise one or more bottles of a cleaning
solution or suspension, such as a liquid skin cleanser. In an
aspect, the cleaning solution or suspension can be Hibiclens.
[0096] In an aspect, the disclosed kit comprises a foot bath
starter pack. The foot bath starter pack may be suitable for
administering one or more of the compounded compositions described
herein, e.g., foot bath compositions and foot bath solutions. In
various aspects, the foot bath starter pack includes a foot bath, 1
to 2 bottle(s) of diluent, a funnel, a mixing container, and a
measuring device for measuring powder medications, e.g., one or two
spoons/scoops, such as those described above.
[0097] In one aspect, the compounded composition includes a
compounded powder comprising about 25% (w/w) mupirocin and about
25% (w/w) itraconazole. The second anti-infective may be an
anti-bacterial agent as described herein. The compounded powder may
also include Loxasperse.RTM.-Xylifos.TM. Combination Powder, which
may make up the remaining 50% of the compounded powder. A method of
treating or preventing an infection, such as a foot infection, with
such a composition using the foot bath starter pack may comprise
filling the foot bath with warm water to a fill line indicated on
the inside of the foot bath. Using the funnel, adding 2 scoops of
medication using a first spoon into the mixing container. For every
tablespoon of powder, 15 ml of diluent may be added to the mixing
container holding the powder. The mixture may then be mixed, e.g.,
by shaking or stirring. The foot bath may then be turned on and the
water therein allowed to agitate. The solution/suspension mixture
may then be added to the water. The subject's foot or portion
thereof may be placed in the foot bath for a suitable amount of
time, such as 10 minutes, or other duration, such as described
elsewhere herein. The foot bath starter pack may be configured for
use in administration of different compounded compositions and foot
bath compositions. For example, in one aspect, a foot bath
composition comprises mupirocin or streptomycin and a second
anti-infective such as itraconazole or colistimethate. The foot
bath compositions may comprises various rations of mupirocin or
streptomycin to the second anti-infective, e.g., between about 1:9
and about 9:1, about 1:1, about 1:2, about 1:3, about 2:1, or about
3:1. A method of treating or preventing an infection, such as a
foot infection, with such a composition using the foot bath starter
pack may comprise filling the foot bath with warm water to a fill
line indicated on the inside of the foot bath. Using the funnel,
adding 2 scoops of mupirocin or streptomycin, e.g., streptomycin
sulfate for injection, powder using a second spoon, different from
the first, and one scoop of the second anti-infective using the
second spoon, may be added into the mixing container. For every
tablespoon of powder, 15 ml of diluent may be added to the mixing
container holding the powder. The mixture may then be mixed, e.g.,
by shaking or stirring. The foot bath may then be turned on and the
water therein allowed to agitate. The solution/suspension mixture
may then be added to the water. The subject's foot or portion
thereof may be placed in the foot bath for a suitable amount of
time, such as 10 minutes, or other duration, such as described
elsewhere herein.
[0098] In a further aspect, the foot bath composition includes a
combination ointment and powder. For example, in one aspect, the
foot bath composition comprises mupirocin 2% ointment, streptomycin
powder, or a compounded streptomycin ointment comprising about 1%
to about 10% streptomycin by weight and an antifungal agent, as
disclosed herein. The antifungal agent may comprise, for example,
one or more of ketoconazole, voriconazole, amphotericin, or
nystatin. The antifungal agent may be a dry powder comprising
crushed oral tablets, bulk powder, antifungal for injection, or
combinations thereof. In one example, the antifungal agent includes
nystatin topical powder. A method of treating or preventing an
infection, such as a foot infection, with such a composition using
the foot bath starter pack may comprise filling the foot bath with
warm water to a fill line indicated on the inside of the foot bath.
The method may further include opening one bottle of nystatin 15 mg
and placing the opening of the bottle into the neck of the mixing
container and squeezing until all the powder is removed from the
bottle. The method may further include opening a tube of mupironcin
2% ointment or compounded streptomycin ointment comprising about 1%
to about 10% streptomycin by weight and emptying at least a portion
of the contents of the tube into the mixing container. The
compounded streptomycin ointment may comprise one or more
additional anti-infectives as described herein or in instances
wherein one or more additional anti-infectives are to be compounded
to formulate the foot bath solution, additional anti-infectives may
be mixed with the ointment, added to the mixing container, added to
the solution/suspension mixture, or added to water or mixed
streptomycin ointment and water in the foot bath. For every
tablespoon of the foot bath composition, 15 ml of diluent may be
added to the mixing container holding the composition. The mixture
may then be mixed, e.g., by shaking or stirring. The foot bath may
then be turned on and the water therein allowed to agitate. The
solution/suspension mixture may then be added to the water. The
subject's foot or portion thereof may be placed in the foot bath
for a suitable amount of time, such as 10 minutes, or other
duration, such as described elsewhere herein.
D. Methods of Making a Compounded Composition
[0099] Disclosed herein is a method of making a compounded
composition, the method comprising: mixing a therapeutically
effective amount of a first anti-infective agent, such as first
antibacterial agent, and a therapeutically effective amount of a
second anti-infective agent, such as one or more antibacterial
agents, one or more anti-funcal agents, or combination thereof
agent to make a homogenous compounded composition. A disclosed
compounded composition can comprise a dry powder formulation or can
comprise an ointment.
[0100] In an aspect, the mixing can comprise using an electronic
mortar and pestle (EMP). In an aspect, a disclosed method can
comprise milling the ingredients (using, for example, a three-roll
mill). Mixing and milling can be done according to standards known
to the skilled person in the art.
[0101] In an aspect, a disclosed method can comprise obtaining the
first antibacterial agent, obtaining the second antibacterial
agent, or a combination thereof In an aspect, obtaining can
comprise obtaining a bulk source of the first antibacterial agent,
obtaining a bulk source of the second antibacterial agent, or a
combination thereof. In an aspect, a disclosed method can comprise
obtaining the antibacterial agent, obtaining the antifungal agent,
or a combination thereof. In an aspect, obtaining can comprise
obtaining a bulk source of one or more antibacterials of the
antibacterial agent or obtaining a bulk source of one or more
antifungals of the antifungal agent. In an aspect, a disclosed
method can comprise obtaining the first antibacterial agent,
obtaining the second antibacterial agent, obtaining the antifungal
agent, or a combination thereof. In an aspect, obtaining can
comprise obtaining a bulk source of the first antibacterial agent,
obtaining a bulk source of the second antibacterial agent,
obtaining a bulk source of the antifungal agent, or a combination
thereof.
[0102] In an aspect, a disclosed method can comprise mixing a
therapeutically effective amount of one or more additional
anti-infective agents with the compounded composition. In an
aspect, the additional anti-infective agent can be an antibacterial
agent. Antibacterial agents are known to the art and discussed
supra. In an aspect, the additional anti-infective agent can be an
antifungal agent. Antifungal agents are known to the art and
discussed supra. In an aspect, a disclosed method can comprise
obtaining the additional anti-infective agent. In an aspect,
obtaining can comprise obtaining a bulk source of the
anti-infective agent.
[0103] In an aspect, a disclosed method can comprise mixing a
compounded ointment or dry powder comprising streptomycin alone or
in combination with one or more additional anti-infectives as
described herein with a diluent. Mixing may be prior to
administration, e.g., at the time of administration. In one
example, one or more additional anti-infectives may comprise
colistimethate, clindamycin, mupirocin, levofloxacin, or
combination thereof. The diluent may comprise a dry powder, cream,
ointment, emulsion (o/w, w/o), gel, jelly, wax, solution. Solutions
may include, for example, water (e.g., potable water, sterile
water, water for injection), aqueous based solutions, oil based
solutions, organic solvents, saline (e.g., 0.9% saline, normal
saline), povidone iodine, sodium hypochlorite (Dakin's solution),
hydrogen peroxide, cleansers (e.g., wound cleansers). The resulting
mixture for administration may comprise between about 1% and about
20% streptomycin. When a second or additional anti-infective is
present, the resulting mixture for administration may include
between about 1% and about 20% second anti-infective by weight.
[0104] In various embodiments, a method of making a compounded
composition comprising a dry powder, topical solution, or other
compounded topical formulation includes formulating the composition
to include an amount of streptomycin configured to provide less
than or equal to 1 gm of delivered streptomycin per day, such as
less than about 25 mg, about 50 mg, about 75 mg, about 100 mg,
about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600
mg, about 700 mg, about 800 mg, or about 900 mg. For example, the
strength of a compounded composition for topical administration
with respect to streptomycin may be determined by the amount of
streptomycin that may be delivered using the desired format and
number of treatments per day. Accordingly, a method of making the
compounded composition may include combining a suitable amount of
diluent to formulate the compounded composition for administration.
Thus, according to at least one embodiment, the compounded
composition may be formulated such that it may be contacted with a
body surface of a subject that is infected or suspected to be
infected with a suitable amount of the compounded composition to
topically deliver between 25 mg and 1 gm of streptomycin per day,
such as between about 25 mg and about 900 mg, about 25 mg and about
500 mg, about 25 mg and about 200 mg, about 50 mg and about 1 gm,
about 50 mg and about 800 mg, about 50 mg and about 500 mg, about
50 mg and about 200 mg, about 100 mg and about 1 gm, about 100 mg
and about 800 mg, about 100 mg and about 500 mg, about 300 mg and
about 1 gm, about 300 mg and about 800 mg, about 300 mg and about
500 mg. about 500 mg and about 1 gm, about 500 mg and about 800 mg,
or about 800 mg and about 1 gm. Accordingly, streptomycin and one
or more additional anti-infectives, when present, may be compounded
with or mixed with a suitable amount of diluent to formulate the
compounded composition for administration. The ratio of second
anti-infective agent, when present, to streptomycin in a compounded
composition, which may include compounded capsules, compounded
ointments, compounded topical compositions obtained by mixing a
compounded composition, such as a compounded capsule or compounded
ointment, with a diluent at the time of administration, may be
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, about 1:10, about 1:12, about
1:14, about 1:15, about 1:20, or less. In various embodiments, the
ratio of the second anti-infective agent to the first
anti-infective agent is between about 1:1 and 1:20, 1:2 and about
1:15, about 1:3 and about 1:15, about 1:3 and about 1:10, about 1:4
and about 1:15, or about 1:4 and about 1:10.
[0105] In an aspect, a disclosed method can comprise mixing one or
more excipients or additives with the compounded composition. In an
aspect, excipients or additives include, but are not limited to,
the following: solvents, surfactants, humectants, preservatives,
flavorings, stabilizers (including antioxidants), binders, and
colorants.
[0106] In various embodiments, a method of making a compounded
composition comprises forming a compounded capsule comprising a dry
powder. In one embodiment, the compounded capsule may include about
50 mg and about 250 mg streptomycin. In further embodiments, the
method may include forming a compounded capsule including a second
anti-infective agent comprising one or more additional
anti-infectives selected from an antibacterial, antifungal, or
combination thereof. The second anti-infective may be present in an
amount less than or greater than the streptomycin. In various
embodiments, the second anti-infective agent may be present in
lesser amount than the streptomycin. For example, the second
anti-infective agent may be present in an amount less than about
100 mg, less than about 75 mg, less than about 50 mg, or less than
about 25 mg. In various embodiments, the method may include forming
a compounded capsule including a second anti-infective agent
comprising an antibacterial selected from colistimethate,
clindamycin, mupirocin, levofloxacin, or combination thereof. In
some embodiments, the method may include combining between about 25
mg and about 100 mg, about 25 mg and about 25 mg, about 25 mg and
about 50 mg, or about 50 mg and about 75 mg of the second
anti-infective with the streptomycin. For example, in one
embodiment, a compounded capsule includes between about 50 mg and
about 225 mg streptomycin and between about 25 and about 75 mg
colistimethate. In another example, a compounded capsule includes
between about 50 mg and about 225 mg streptomycin and between about
25 mg and about 50 mg mupirocin.In one embodiment, a method of
making a compounded capsule comprises combining streptomycin
sulfate for injection with a base, such as PCCA Loxasperse. In one
example, a compounded capsule comprising 225 mg of streptomycin may
be formulated by combining 310.95 mg of streptomycin sulfate for
injection with 5 mg of PCCA Loxasperse. The streptomycin sulfate
for injection may be obtained from 1 g streptomycin vials of
streptomycin sulfate for injection, which contained about 1.382 gm
streptomycin sulfate. The method may further include combining a
second anti-infective in an amount less than about 100 mg, less
than about 75 mg, less than about 50 mg, or less than about 25 mg.
Depending on the size of the capsule, the amount of streptomycin
may be reduced by an amount equivalent to the amount of second
anti-infective. In various embodiments, the method may include
combining between about 25 mg and about 100 mg, about 25 mg and
about 25 mg, about 25 mg and about 50 mg, or about 50 mg and about
75 mg of the second anti-infective with the streptomycin wherein
the second anti-infective agent comprises an antibacterial selected
from colistimethate, clindamycin, mupirocin, levofloxacin, or
combination thereof. In one embodiment, the method includes
combining between about 50 mg and about 225 mg streptomycin (or an
equivalent amount of streptomycin sulfate for injection) and
between about 25 and about 75 mg colistimethate. In another
example, the method includes combining between about 50 mg and
about 225 mg streptomycin (or an equivalent amount of streptomycin
sulfate for injection) and between about 25 mg and about 50 mg
mupirocin. The second anti-infectives may comprise a dry powder
obtained from bulk powder, crushed tablets, or powder for
injection.
[0107] In an aspect, a disclosed method can comprise mixing a
therapeutically effective amount of one or more additional
anti-infective agents with the compounded composition. In an
aspect, the additional anti-infective agent can be an antibacterial
agent. Antibacterial agents are known to the art and discussed
supra. In an aspect, the additional anti-infective agent can be an
antifungal agent. Antifungal agents are known to the art and
discussed supra. In an aspect, a disclosed method can comprise
obtaining the additional anti-infective agent. In an aspect,
obtaining can comprise obtaining a bulk source of the
anti-infective agent.
[0108] In an aspect, a disclosed method can comprise packaging the
compounded composition into a container and sealing the container.
In an aspect, a container can be a container disclosed herein, such
as, for example, a plastic tube, a glass or non-glass vial, a
syringe, etc. In an aspect, a disclosed method can comprise
sterilizing the compounded composition.
[0109] In an aspect, a disclosed method can comprise mixing one or
more excipients or additives with the compounded composition. In an
aspect, excipients or additives include, but are not limited to,
the following: solvents, surfactants, humectants, preservatives,
flavorings, stabilizers (including antioxidants), binders, and
colorants.
[0110] In an aspect, a disclosed method can comprise packaging the
compounded composition comprising a first antibacterial agent, a
second antibacterial agent, and an antifungal agent into a
container and sealing the container. In an aspect, a container can
be a container disclosed herein, such as, for example, a plastic
tube, a glass or non-glass vial, a syringe, etc. In an aspect, a
disclosed method can comprise sterilizing the compounded
composition comprising a first antibacterial agent, a second
antibacterial agent, and an antifungal agent.
E. Methods of Treating or Preventing an Infection Using a
Compounded Composition
[0111] Disclosed herein is a method of treating or preventing an
infection, the method comprising: applying to the skin of a subject
a compounded composition, wherein the compounded composition
comprises any compounded composition disclosed herein.
[0112] Disclosed herein is a method of treating or preventing an
infection, the method comprising: preparing a homogenous compounded
composition comprising any compounded composition disclosed
herein.
[0113] In an aspect, a disclosed method can comprise orally
administering to the subject a pharmaceutical composition
comprising one or more additional anti-infective agents. In an
aspect, the additional anti-infective agent can be an antibacterial
agent, such as any suitable antibacterial agent, e.g., any suitable
antibacterial listed herein. In an aspect, the additional
anti-infective agent can be an antifungal agent, such as any
suitable antifungal agent, e.g., any suitable antifungal agent
listed herein.
[0114] In an aspect, a disclosed method can comprise pre-treating
the subject's hands. In an aspect, a subject can apply a liquid
skin cleanser (e.g., Hibiclens) to his hands. Using water, the
subject can wash his hands with the Hibiclens for at least 5
seconds, at least 10 seconds, at least 15 seconds, at least 20
seconds, or at least 30 seconds.
[0115] In an aspect, a disclosed method can comprise repeating the
applying step until the bacterial infection, suspected bacterial
infection, the fungal infection, or the suspected fungal infection
is eradicated or appears to be eradicated. In an aspect, a
disclosed method can comprise repeating the applying step twice
daily until the bacterial infection, suspected bacterial infection,
the fungal infection, or the suspected fungal infection is
eradicated or appears to be eradicated. In an aspect, a disclosed
method can comprise repeating the applying step twice daily for a
pre-determined amount of time. In an aspect, the pre-determined
amount of time can comprise at least 5 days, at least 7 days, at
least 10 days, at least 14 days, at least 21 days, at least 30
days, or more than 30 days. In an aspect, the pre-determined amount
can comprise an amount of time lasting at least 5-7 days, at least
7-10 days, at least 10-14 days, at least 14-21 days, at least 21-30
days, at least 30 days, or more than 30 days.
[0116] In an aspect, applying the compounded composition can
comprise contacting the compounded composition with the subject's
skin until the compounded composition has been absorbed or
substantially absorbed by the skin. In an aspect, applying can
comprise using a sterile applicator to contact the compounded
composition with the skin. In an aspect, applying can comprise
contacting about 2 g to about 6 g, or about 3 g to about 5 g, or
about 4 g of the compounded composition with the subject's skin. In
an aspect, a disclosed compounded composition can be applied to
skin in conjunction with an occlusive dressing. In an aspect, a
disclosed method can comprise applying a covering to the skin
affected by the infection.
[0117] In an aspect, a disclosed compounded composition can be
mixed with a diluent to form a solution or suspension and then
applied to the subject's skin. Diluents are discussed supra. In an
aspect, a disclosed compounded composition and the diluent can be
mixed in a mixing container. In an aspect, a mixing container can
have a pre-determined size that can measure or hold a
pre-determined amount or volume. In an aspect, a mixing container
can measure or hold about 30 mL to about 300 mL. In an aspect, the
mixing container can hold about 30 mL, about 60 mL, about 90 mL,
about 120 mL, about 150 mL, about 180 mL, about 210 mL, about 240
mL, about 270 mL, or about 300 mL. In an aspect, the mixing
container can hold about 180 mL. In an aspect, a disclosed method
can comprise cleaning and drying a mixing container.
[0118] In an aspect, a disclosed compounded composition can be
applied to the subject's skin as a dry powder or as an ointment. In
an aspect, a disclosed compounded composition can be applied to the
subject's skin as a cream, or lotion, or emulsion, or gel. For
example, the compounded composition may comprise a compounded
ointment of any disclosed compounded composition formulated in an
ointment as described herein.
[0119] In one embodiment, a method of treating an infection
comprises applying to infected skin a compounded composition
ointment comprising a therapeutically effective amount of mupirocin
ointment (e.g., mupirocin 2% ointment) and a therapeutically
effective amount of an antibacterial agent comprising one or more
antibacterials or pharmaceutically acceptable salt thereof selected
from bacitracin, colistimethate, piperacillin-tazobactam, polymyxin
B, streptomycin, or combinations thereof. All or a portion of the
antibacterial agent may comprise anti-infective for injection
powder compounded with the mupirocin ointment. In this or another
embodiment, a method of treating an infection comprises applying to
infected skin a compounded composition comprising a therapeutically
effective amount of a compounded composition comprising
streptomycin alone or in combination with one or more additional
anti-infectives as described. In one example, one or more
additional anti-infectives may comprise colistimethate,
clindamycin, mupirocin, levofloxacin, or combination thereof. All
or a portion of the streptomycin and anti-infectives may be
obtained from anti-infective for injection powders, tablets, or
bulk powders. The compounded composition may be in various formats
such as a dry powder, cream, ointment, emulsion (o/w, w/o), gel,
jelly, wax, solution. Solutions may include, for example, water
(e.g., potable water, sterile water, water for injection), aqueous
based solutions, oil based solutions, organic solvent based
solutions, saline solutions (e.g., 0.9% saline, normal saline),
povidone iodine solutions, sodium hypochlorite solution (Dakin's
solution), hydrogen peroxide solutions, or cleansers (e.g., wound
cleansers).
[0120] In various embodiments, a method of making of treating an
infection of suspected infection with a compounded composition
described herein comprising a dry powder, topical solution, or
other compounded topical formulation includes formulating the
composition to include an amount of streptomycin configured to
provide less than or equal to 1 gm of delivered streptomycin per
day, such as less than about 25 mg, about 50 mg, about 75 mg, about
100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg,
about 600 mg, about 700 mg, about 800 mg, or about 900 mg. For
example, the strength of a compounded composition for topical
administration with respect to streptomycin and amount to be
administered may be determined by the amount of streptomycin that
may be delivered using the desired format and number of treatments
per day.
[0121] Accordingly, a method of treating and infection or suspected
infection may include combining a suitable amount of diluent to
formulate the compounded composition for administration and/or
administering a suitable amount of compounded composition to
deliver between 25 mg and 1 gm of streptomycin per day. Thus,
according to at least one embodiment, the compounded composition
may be formulated such that it may be contacted with a body surface
of a subject that is infected or suspected to be infected with a
suitable amount of the compounded composition to topically deliver
between 25 mg and 1 gm of streptomycin per day, such as between
about 25 mg and about 900 mg, about 25 mg and about 500 mg, about
25 mg and about 200 mg, about 50 mg and about 1 gm, about 50 mg and
about 800 mg, about 50 mg and about 500 mg, about 50 mg and about
200 mg, about 100 mg and about 1 gm, about 100 mg and about 800 mg,
about 100 mg and about 500 mg, about 300 mg and about 1 gm, about
300 mg and about 800 mg, about 300 mg and about 500 mg. about 500
mg and about 1 gm, about 500 mg and about 800 mg, or about 800 mg
and about 1 gm. Accordingly, streptomycin and one or more
additional anti-infectives, when present, may be compounded with or
mixed with a suitable amount of diluent to formulate the compounded
composition for administration. The ratio of second anti-infective
agent, when present, to streptomycin in a compounded composition,
which may include compounded capsules, compounded ointments,
compounded topical compositions obtained by mixing a compounded
composition, such as a compounded capsule or compounded ointment,
with a diluent at the time of administration, may be 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, about 1:10, about 1:12, about 1:14, about
1:15, about 1:20, or less. In various embodiments, the ratio of the
second anti-infective agent to the first anti-infective agent is
between about 1:1 and 1:20, 1:2 and about 1:15, about 1:3 and about
1:15, about 1:3 and about 1:10, about 1:4 and about 1:15, or about
1:4 and about 1:10.
[0122] In an aspect, the subject can be diagnosed with or can be
suspected of having a bacterial infection or a fungal infection
that affects the subject's skin. In an aspect, the subject can have
diabetes, can be obese, can be immunocompromised, can be
non-ambulatory, or can have poor blood flow, or a combination
thereof. In an aspect, the subject can routinely wear thick socks
or wear heavy boots.
[0123] In an aspect, a disclosed method can comprise preparing a
disclosed compounded composition. Disclosed and discussed supra are
methods of preparing a disclosed compounded composition, such as,
for example, wherein the compounded composition comprises (1) a
therapeutically effective amount of a first antibacterial agent and
a therapeutically effective amount of a second antibacterial agent,
(2) a therapeutically effective amount of an antibacterial agent
and a therapeutically effective amount of an antifungal agent, (3)
a therapeutically effective amount of a first antibacterial agent,
a therapeutically effective amount of a second antibacterial agent,
and a therapeutically effective amount of an antifungal agent, (4)
a therapeutically effective amount of mupirocin and a
therapeutically effective amount of an antibacterial agent, (5) a
therapeutically effective amount of mupirocin and a therapeutically
effective amount of tobramycin or a pharmaceutically acceptable
salt thereof, (6) a therapeutically effective amount of mupirocin
and a therapeutically effective amount of an antibacterial agent
comprising one or more antibacterials or pharmaceutically
acceptable salt thereof selected from bacitracin, colistimethate,
piperacillin-tazobactam, polymyxin B, streptomycin, or combinations
thereof, (8) a therapeutically effective amount of streptomycin and
a therapeutically effective amount of an additional anti-infective,
(9) a therapeutically effective amount of streptomycin and a
therapeutically effective amount of an additional anti-infective
comprising colistimethate, clindamycin, mupirocin, levofloxacin, or
combination thereof.
[0124] In an aspect, a disclosed method of treating or preventing
an infection can comprise modifying one or more aspect of the
disclosed method. For example, in an aspect, a disclosed method can
comprise changing or altering the amount of the disclosed
compounded composition applied to a subject's skin, or by changing
the frequency of the subject's use of the compounded composition,
or by changing the duration of time that the subject uses the
compounded composition, or by substituting one compounded
composition for another compounded composition, or a combination
thereof.
F. Methods of Treating or Preventing a Foot Infection Using a
Compounded Composition
[0125] Disclosed herein is a method of treating or preventing a
foot infection, the method comprising: (i) adding a compounded
composition to water contained within a foot bath; (ii) agitating
the water contained within the foot bath; and (iii) contacting the
agitated water with at least a part of one or both feet of a
subject.
[0126] Disclosed herein is a method of treating or preventing a
foot infection, the method comprising: (i) agitating water
contained within a foot bath; (ii) adding a compounded composition
to the water contained with the foot bath; and (iii) contacting the
agitated water with at least a part of one or both feet of a
subject.
[0127] Disclosed herein is a method of treating or preventing a
foot infection, the method comprising: (i) mixing a compounded
composition with a diluent to create a solution or suspension; (ii)
adding the solution or suspension to water contained within a foot
bath; (iii) agitating the water contained within the foot bath; and
(iv) contacting the agitated water with at least part of one or
both feet of a subject.
[0128] Disclosed herein is a method of treating or preventing a
foot infection, the method comprising: (i) mixing a compounded
composition with a diluent to create a solution or suspension; (ii)
agitating water contained within a foot bath; (iii) adding the
solution or suspension to the water contained within the foot bath;
and (iv) contacting the agitated water with at least part of one or
both feet of a subject.
[0129] Disclosed herein is a method of treating or preventing a
foot infection, the method comprising: (i) adding a compounded
composition to water contained within a foot bath; (ii) agitating
the water contained within the foot bath; and (iii) contacting the
agitated water with at least a part of one or both feet of a
subject, wherein the compounded composition comprises (1) a
therapeutically effective amount of a first antibacterial agent and
a therapeutically effective amount of a second antibacterial agent,
(2) a therapeutically effective amount of an antibacterial agent
and a therapeutically effective amount of an antifungal agent, (3)
a therapeutically effective amount of a first antibacterial agent,
a therapeutically effective amount of a second antibacterial agent,
and a therapeutically effective amount of an antifungal agent, (4)
a therapeutically effective amount of mupirocin and a
therapeutically effective amount of an antibacterial agent, (5) a
therapeutically effective amount of mupirocin and a therapeutically
effective amount of tobramycin or a pharmaceutically acceptable
salt thereof, (6) a therapeutically effective amount of mupirocin
and a therapeutically effective amount of an antibacterial agent
comprising one or more antibacterials or pharmaceutically
acceptable salt thereof selected from bacitracin, colistimethate,
piperacillin-tazobactam, polymyxin B, streptomycin, or combinations
thereof, (8) a therapeutically effective amount of streptomycin and
a therapeutically effective amount of an additional anti-infective,
(9) a therapeutically effective amount of streptomycin and a
therapeutically effective amount of an additional anti-infective
comprising colistimethate, clindamycin, mupirocin, levofloxacin, or
combination thereof.
[0130] Disclosed herein is a method of treating or preventing a
foot infection, the method comprising: (i) agitating water
contained within a foot bath; (ii) adding a compounded composition
to the water contained within the foot bath; and (iii) contacting
the agitated water with at least a part of one or both feet of a
subject. The compounded composition may be any compounded
composition, e.g., compounded ointment, described herein.
[0131] Disclosed herein is a method of treating or preventing a
foot infection, the method comprising: (i) mixing a compounded
composition with a diluent to create a solution or suspension; (ii)
adding the solution or suspension to water contained within a foot
bath; (iii) agitating the water contained within the foot bath; and
(iv) contacting the agitated water with at least part of one or
both feet of a subject, wherein the compounded composition
comprises (1) a therapeutically effective amount of a first
antibacterial agent and a therapeutically effective amount of a
second antibacterial agent, (2) a therapeutically effective amount
of an antibacterial agent and a therapeutically effective amount of
an antifungal agent, (3) a therapeutically effective amount of a
first antibacterial agent, a therapeutically effective amount of a
second antibacterial agent, and a therapeutically effective amount
of an antifungal agent, (4) a therapeutically effective amount of
mupirocin and a therapeutically effective amount of an
antibacterial agent, (5) a therapeutically effective amount of
mupirocin and a therapeutically effective amount of tobramycin or a
pharmaceutically acceptable salt thereof, (6) a therapeutically
effective amount of mupirocin and a therapeutically effective
amount of an antibacterial agent comprising one or more
antibacterials or pharmaceutically acceptable salt thereof selected
from bacitracin, colistimethate, piperacillin-tazobactam, polymyxin
B, streptomycin, or combinations thereof, (8) a therapeutically
effective amount of streptomycin and a therapeutically effective
amount of an additional anti-infective, (9) a therapeutically
effective amount of streptomycin and a therapeutically effective
amount of an additional anti-infective comprising colistimethate,
clindamycin, mupirocin, levofloxacin, or combination thereof.
[0132] Disclosed herein is a method of treating or preventing a
foot infection, the method comprising: (i) mixing a compounded
composition with a diluent to create a solution or suspension; (ii)
agitating water contained within a foot bath; (iii) adding the
solution or suspension to the water contained within the foot bath;
and (iv) contacting the agitated water with at least part of one or
both feet of a subject, wherein the compounded composition
comprises (1) a therapeutically effective amount of a first
antibacterial agent and a therapeutically effective amount of a
second antibacterial agent, (2) a therapeutically effective amount
of an antibacterial agent and a therapeutically effective amount of
an antifungal agent, (3) a therapeutically effective amount of a
first antibacterial agent, a therapeutically effective amount of a
second antibacterial agent, and a therapeutically effective amount
of an antifungal agent, (4) a therapeutically effective amount of
mupirocin and a therapeutically effective amount of an
antibacterial agent, (5) a therapeutically effective amount of
mupirocin and a therapeutically effective amount of tobramycin or a
pharmaceutically acceptable salt thereof, (6) a therapeutically
effective amount of mupirocin and a therapeutically effective
amount of an antibacterial agent comprising one or more
antibacterials or pharmaceutically acceptable salt thereof selected
from bacitracin, colistimethate, piperacillin-tazobactam, polymyxin
B, streptomycin, or combinations thereof, (8) a therapeutically
effective amount of streptomycin and a therapeutically effective
amount of an additional anti-infective, (9) a therapeutically
effective amount of streptomycin and a therapeutically effective
amount of an additional anti-infective comprising colistimethate,
clindamycin, mupirocin, levofloxacin, or combination thereof.
[0133] In an aspect, a disclosed method can treat or prevent an
infection affecting the skin of at least a portion of a subject's
foot or feet. In an aspect, a disclosed method can treat or prevent
an infection affecting the nail of at least one toe on a subject's
foot or feet.
[0134] In an aspect, the subject can have diabetes, can be obese,
can be immunocompromised, can be non-ambulatory, or can have poor
blood flow, or a combination thereof In an aspect, the subject can
routinely wear thick socks or wear heavy boots. In an aspect, the
subject has been diagnosed with or is suspected of having a
bacterial infection that affects at least part of one or both feet.
In an aspect, the subject has been diagnosed with or is suspected
of having a bacterial infection and a fungal infection that affect
at least part of one or both feet. In an aspect, the subject has
been diagnosed with or is suspected of having a fungal infection
that affects at least part of one or both feet.
[0135] In an aspect, a disclosed method can comprise orally
administering to the subject a pharmaceutical composition
comprising one or more anti-infective agents. In an aspect, the
additional anti-infective agent can be an antibacterial agent.
Antibacterial agents are known to the art and discussed supra. In
an aspect, the additional anti-infective agent can be an antifungal
agent. Antifungal agents are known to the art and discussed
supra.
[0136] In an aspect, adding a disclosed compounded composition to
the water contained within a foot bath can comprise adding to the
water between about 10 g to about 40 g of a disclosed compounded
composition, or about 20 g to about 30 g of a disclosed compounded
composition, or about 25 g of a disclosed compounded
composition.
[0137] In an aspect, a disclosed compounded composition and the
diluent can be mixed in a mixing container. In an aspect, a mixing
container can have a pre-determined size that can measure or hold a
pre-determined amount or volume. In an aspect, a mixing container
can measure or hold about 30 mL to about 300 mL. In an aspect, the
mixing container can hold about 30 mL, about 60 mL, about 90 mL,
about 120 mL, about 150 mL, about 180 mL, about 210 mL, about 240
mL, about 270 mL, or about 300 mL. In an aspect, the mixing
container can hold about 180 mL.
[0138] In an aspect, a disclosed method can comprise adding the
diluent to the water contained in the foot bath. In an aspect, the
diluent can comprise sodium hypochlorite. In an aspect, the diluent
can comprise Dakin's solution. In an aspect, the amount of diluent
can be about 20 mL to about 60 mL, or about 30 to about 50 mL, or
about 20 mL, or about 30 mL, or about 40 mL, or about 50 mL, or
about 60 mL.
[0139] In an aspect, adding the solution or suspension comprising
the compounded composition and the diluent can be added to the foot
bath already having water, thereby increasing the water level in
the foot bath.
[0140] In an aspect, a disclosed method can comprise heating the
water contained within the foot bath. In an aspect, a disclosed
method can comprise agitating the water contained within the foot
bath. In an aspect, a foot bath can comprise a mechanical agitation
agent to mechanically agitate the enclosed water, a heating agent
to heat the enclosed water, or both. Mechanical agitation agents
and/or means to agitate water within a compartment are known to the
art. In an aspect, a mechanical agitation agent can be a motorized
agitation agent. In an aspect, an agitation agent or an agitator
can be coupled to both a motor and the foot bath. Motors and
agitators are known to the art. In an aspect, mechanical agitation
can serve to distribute the compounded composition, the diluent, or
the solution or suspension comprising the compounded composition
and the diluent throughout the water contained within the foot
bath. Heating agents and/or means to heat water in a compartment
are known to the art.
[0141] In an aspect of a disclosed method, a disclosed compound
composition can be added to the water contained within the foot
bath while the water is being heated. In an aspect of a disclosed
method, a disclosed compound composition can be added to the water
contained within the foot bath while the water is being
agitated.
[0142] In an aspect, agitation can ensure dissolution of the
compounded composition or the dissolution of solution or suspension
comprising the compounded composition.
[0143] In an aspect, agitation can ensure optimal contact of the
compounded composition with at least a part of the subject's foot
or feet.
[0144] In an aspect, a disclosed method can comprise repeating
daily steps (i)-(iii) or steps (i)-(iv). In an aspect, a disclosed
method can comprise repeating daily steps (i)-(iii) or steps
(i)-(iv) until the bacterial infection, suspected bacterial
infection, the fungal infection, or the suspected fungal infection
is eradicated or appears to be eradicated. In an aspect, a
disclosed method can comprise repeating twice daily the applying
step for a pre-determined amount of time. In an aspect, the
pre-determined amount of time can comprise at least 5 days, at
least 7 days, at least 10 days, at least 14 days, at least 21 days,
at least 30 days, or more. In an aspect, the pre-determined amount
can comprise an amount of time lasting at least 5-7 days, at least
7-10 days, at least 10-14 days, at least 14-21 days, at least 21-30
days, or at least 30 days.
[0145] In an aspect, contacting can comprise placing at least part
of one or both feet of the subject in the foot bath. In an aspect,
contacting can comprise placing at least part of one or both feet
of the subject in the foot bath for about 5 to about 15 minutes. In
an aspect, contacting can comprise placing at least part of one or
both feet of the subject in the foot bath for about 10 minutes.
[0146] In an aspect, the method can comprise removing the
compounded composition from a container, such as, for example, a
tube, a packet, a capsule, a syringe, a vial, etc., prior to adding
the compounded composition to the water. In an aspect, the method
can comprise removing the compounded composition from a container,
such as, for example, a tube, a packet, a capsule, a syringe, a
vial, etc., prior to adding the composition to the diluent. In an
aspect, a capsule can be broken apart and the contents of the
capsule can be added to the water in the foot bath. In an aspect,
an intact capsule can be added to the water in the foot bath.
[0147] In an aspect, a disclosed method can comprise emptying the
water from the foot bath. In an aspect, a disclosed method can
comprise cleaning the foot bath. In an aspect, a disclosed method
can comprise drying the foot bath.
[0148] In an aspect, a disclosed method can comprise preparing a
disclosed compounded composition. Methods of preparing a disclosed
compounded composition are discussed supra.
[0149] In an aspect, a disclosed method of treating or preventing a
foot infection can comprise modifying one or more aspect of the
disclosed method. For example, in an aspect, a method can be
altered by changing the amount of a disclosed compounded
composition added to a foot bath, by changing the frequency of the
subject's use of the foot bath, or by changing the duration of time
that the subject's foot or feet contact the water contained within
the foot bath, or by substituting one disclosed compounded
composition for another disclosed compounded composition, or a
combination thereof.
[0150] In various aspects, a method of treating or preventing an
infection, such as a foot infection, may comprise making or
administering any of the disclosed compounded compositions to an
affected skin surface of a subject. In some aspects, the compounded
composition comprises a foot bath composition for application to a
foot of a subject. In one aspect, any of the disclosed compounded
compositions may be administered in a foot bath solution. For
example, added into a mixing container along with a suitable amount
of diluent.
[0151] The composition may be provided in a syringe, for example,
for ease of addition with the diluent. The contents (e.g., 25 g)
may be added to a suitable amount of diluent, as described herein,
and mixed, e.g., in a mixing container. The amount of diluent may
be about 15 ml diluent per tablespoon of the ointment. Other ratios
may be used, e.g., between about 10 ml and about 50 ml, about 10 ml
and about 40 ml, about 10 ml and about 30 ml, about 10 ml and about
20 ml, about 10 ml and about 15 ml, about 15 ml and about 50 ml,
about 15 ml and about 40 ml, about 15 ml and about 30 ml, about 10
ml and about 25 ml, about 15 ml and about 20 ml, about 20 ml and
about 50 ml, about 20 ml and about 40 ml, about 20 ml and about 30
ml, or about 20 ml and about 25 ml. Furthermore, the compounded
composition ointment may be formulated with higher or lower
concentrations of actives in the ointment and amounts of the
compounded composition ointment added to diluent for administration
may thereby adjusted accordingly. Mixing may include shaking or
stirring to form a foot bath solution. In a further aspect, the
foot bath solution may be further agitated. In one aspect, the
mixing container comprises a foot bath. In another aspect, the
contents of the mixing container may be added to a foot bath.
Administering the foot bath solution may include placement of the
foot (or feet) to be treated into the solution. The foot or portion
to be treated thereof may be soaked, e.g., submerged, in the bath
for a suitable period of time, e.g., between about 5 minutes and
about 25 minutes, between about 5 minutes and about 20 minutes,
about 5 minutes and about 15 minutes, about 5 minutes and about 10
minutes, between about 10 minutes and about 25 minutes, about 10
minutes and about 20 minutes, about 10 minutes and about 15
minutes, between about 15 minutes and about 25 minutes, about 15
minutes and about 20 minutes, or about 20 minutes and about 25
minutes. Administration may be repeated as directed, e.g., once
daily.
[0152] In various aspects, the method of treating or preventing a
foot infection may include making or administering any of the above
foot bath compositions or solutions to a subject and further
dispensing or administering up to about 2 g urea 40% cream or
equivalent thereof to the affected area two times daily as directed
(up to about 4 g per day) and applying up to about 4 g fluocinonide
0.1% cream to the affected area two times daily as directed (up to
about 8 g per day). In another aspect, the method of treating or
preventing a foot infection may include making or administering any
of the above foot bath compositions or solutions to a subject and
further dispensing or administering up to about 2 g urea 40% cream
or equivalent thereof to the affected area two times daily as
directed (up to about 4 g per day) and applying up to about 3 g of
clobetasol 0.05% ointment to the affected area two times daily as
directed (up to about 6 g per day).
[0153] In various aspects, the method of treating or preventing an
infection, such as a foot infection, may include making or
administering any of the above foot bath compositions or solutions
to a subject and further dispensing or administering up to about 2
g urea 40% cream or equivalent thereof to the affected area two
times daily as directed (up to about 4 g per day) and applying up
to about 4 g fluocinonide 0.1% cream to the affected area two times
daily as directed (up to about 8 g per day). In another aspect, the
method of treating or preventing a foot infection may include
making or administering any of the above foot bath compositions or
solutions to a subject and further dispensing or administering up
to about 2 g urea 40% cream or equivalent thereof to the affected
area two times daily as directed (up to about 4 g per day) and
applying up to about 3 g of clobetasol 0.05% ointment to the
affected area two times daily as directed (up to about 6 g per
day).
[0154] In one aspect, a method of treating or preventing a foot
infection, such as a foot infection, may comprise making or
administering any of the above foot bath compositions or solutions.
In one example, the contents of a capsule may be added to a mixing
container along with a suitable amount of diluent. The contents may
be mixed, e.g., shaken or stirred, to form a foot bath solution. In
a further aspect, the foot bath solution may be further agitated.
In one aspect, the mixing container comprises a foot bath. In
another aspect, the contents of the mixing container may be added
to a foot bath. Administering the foot bath solution may include
placement of the foot (or feet) to be treated into the solution.
The foot or portion to be treated thereof may be soaked, e.g.,
submerged, in the bath for a suitable period of time, e.g., between
about 5 minutes and about 25 minutes, between about 5 minutes and
about 20 minutes, about 5 minutes and about 15 minutes, about 5
minutes and about 10 minutes, between about 10 minutes and about 25
minutes, about 10 minutes and about 20 minutes, about 10 minutes
and about 15 minutes, between about 15 minutes and about 25
minutes, about 15 minutes and about 20 minutes, or about 20 minutes
and about 25 minutes. Administration may be repeated as directed,
e.g., once daily.
[0155] In various aspects, the method of treating or preventing and
infection, such as a foot infection, may include making or
administering any of the above foot bath compositions or solutions
to a subject and further dispensing or administering up to about 2
g urea 40% cream or equivalent thereof to the affected area two
times daily as directed (up to about 4 g per day) and applying up
to about 4 g fluocinonide 0.1% cream to the affected area two times
daily as directed (up to about 8 g per day). In another aspect, the
method of treating or preventing a foot infection may include
making or administering any of the above foot bath compositions or
solutions to a subject and further dispensing or administering up
to about 2 g urea 40% cream or equivalent thereof to the affected
area two times daily as directed (up to about 4 g per day) and
applying up to about 3 g of clobetasol 0.05% ointment to the
affected area two times daily as directed (up to about 6 g per
day).
G. Methods of Treating or Preventing an Infection Using an
Intranasally Administered Compounded Composition
[0156] Disclosed herein is a method of treating or preventing an
infection, the method comprising: (i) intranasally administering to
a subject a solution or suspension comprising a compounded
composition. Disclosed herein is a method of treating or preventing
an infection, the method comprising: (i) mixing a compounded
composition with a diluent to create a solution or suspension; and
(ii) intranasally administering to a subject the solution or
suspension.
[0157] Disclosed herein is a method of treating or preventing an
infection, the method comprising: (i) intranasally administering to
a subject a solution or suspension comprising a compounded
composition, wherein the compounded composition comprises (1) a
therapeutically effective amount of a first antibacterial agent and
a therapeutically effective amount of a second antibacterial agent,
(2) a therapeutically effective amount of an antibacterial agent
and a therapeutically effective amount of an antifungal agent, (3)
a therapeutically effective amount of a first antibacterial agent,
a therapeutically effective amount of a second antibacterial agent,
and a therapeutically effective amount of an antifungal agent, (4)
a therapeutically effective amount of mupirocin and a
therapeutically effective amount of an antibacterial agent, (5) a
therapeutically effective amount of mupirocin and a therapeutically
effective amount of tobramycin or a pharmaceutically acceptable
salt thereof, (6) a therapeutically effective amount of mupirocin
and a therapeutically effective amount of an antibacterial agent
comprising one or more antibacterials or pharmaceutically
acceptable salt thereof selected from bacitracin, colistimethate,
piperacillin-tazobactam, polymyxin B, streptomycin, or combinations
thereof, (8) a therapeutically effective amount of streptomycin and
a therapeutically effective amount of an additional anti-infective,
(9) a therapeutically effective amount of streptomycin and a
therapeutically effective amount of an additional anti-infective
comprising colistimethate, clindamycin, mupirocin, levofloxacin, or
combination thereof.
[0158] Disclosed herein is a method of treating or preventing an
infection, the method comprising: (i) mixing a compounded
composition with a diluent to create a solution or suspension; and
(ii) intranasally administering to a subject the solution or
suspension, wherein the compounded composition comprises (1) a
therapeutically effective amount of a first antibacterial agent and
a therapeutically effective amount of a second antibacterial agent,
(2) a therapeutically effective amount of an antibacterial agent
and a therapeutically effective amount of an antifungal agent, (3)
a therapeutically effective amount of a first antibacterial agent,
a therapeutically effective amount of a second antibacterial agent,
and a therapeutically effective amount of an antifungal agent, (4)
a therapeutically effective amount of mupirocin and a
therapeutically effective amount of an antibacterial agent, (5) a
therapeutically effective amount of mupirocin and a therapeutically
effective amount of tobramycin or a pharmaceutically acceptable
salt thereof, (6) a therapeutically effective amount of mupirocin
and a therapeutically effective amount of an antibacterial agent
comprising one or more antibacterials or pharmaceutically
acceptable salt thereof selected from bacitracin, colistimethate,
piperacillin-tazobactam, polymyxin B, streptomycin, or combinations
thereof, (8) a therapeutically effective amount of streptomycin and
a therapeutically effective amount of an additional anti-infective,
(9) a therapeutically effective amount of streptomycin and a
therapeutically effective amount of an additional anti-infective
comprising colistimethate, clindamycin, mupirocin, levofloxacin, or
combination thereof.
[0159] In an aspect, the subject can have diabetes, can be obese,
can be immunocompromised, can be non-ambulatory, or can have poor
blood flow, or a combination thereof In an aspect, the subject has
been diagnosed with or can be suspected of having (i) cancer that
affects at least a part of the respiratory tract, (ii) emphysema,
(iii) pneumonia, (iv) bronchitis, (v) tuberculosis, (vi) asthma, or
(vii) a combination thereof In an aspect, the subject has been
diagnosed with or is suspected of having a bacterial infection that
affects at least a part of the subject's respiratory tract or a
respiratory organ. In an aspect, the subject has been diagnosed
with or is suspected of having a bacterial infection and a fungal
infection that affect at least a part of the subject's respiratory
tract or a respiratory organ. In an aspect, the subject has been
diagnosed with or is suspected of having a fungal infection that
affects at least one part of the subject's respiratory tract or a
respiratory organ.
[0160] In an aspect, a disclosed method can comprise orally
administering to the subject a pharmaceutical composition
comprising one or more anti-infective agents. In an aspect, the
additional anti-infective agent can be an antibacterial agent.
Antibacterial agents are known to the art and discussed supra. In
an aspect, the additional anti-infective agent can be an antifungal
agent. Antifungal agents are known to the art and discussed
supra.
[0161] In an aspect, mixing the compounded composition with the
diluent can comprise adding about 1 g to about 30 g of the
compounded composition to the diluent. In an aspect, mixing the
compounded composition with the diluent can comprise adding about 1
g, or about 5 g, or about 10 g, or about 15 g, or about 20 g, or
about 25 g, or about 30 g of the compounded composition to the
diluent. In an aspect, mixing the compounded composition to the
diluent can comprise adding about 10 g and about 20 g, about 15 g
and about 30 g, about 20 g and about 30 g, or about 22 g and about
27 g of the compounded composition with the diluent.
[0162] In an aspect, a disclosed compounded composition and the
diluent can be mixed in a mixing container. In an aspect, a mixing
container can have a pre-determined size that can measure or hold a
pre-determined amount or volume. In an aspect, a mixing container
can measure or hold about 30 mL to about 300 mL. In an aspect, the
mixing container can hold about 30 mL, about 60 mL, about 90 mL,
about 120 mL, about 150 mL, about 180 mL, about 210 mL, about 240
mL, about 270 mL, or about 300 mL. In an aspect, the mixing
container can hold about 180 mL.
[0163] In an aspect, the diluent can comprise sodium hypochlorite.
In an aspect, the diluent can comprise Dakin's solution. In an
aspect, the amount of diluent can be about 20 mL to about 60 mL, or
about 30 to about 50 mL, or about 20 mL, or about 30 mL, or about
40 mL, or about 50 mL, or about 60 mL.
[0164] In an aspect, a disclosed method can comprise repeating
daily the administering step. In an aspect, a disclosed method can
comprise repeating daily the administering step until the bacterial
infection or suspected bacterial infection or the fungal infection
or the suspected fungal infection is eradicated or appears to be
eradicated.
[0165] In an aspect, a disclosed method can comprise repeating
daily the mixing step or the administering step or repeating both
steps. In an aspect, a disclosed method can comprise repeating
daily the mixing step or the administering step or reporting both
the steps until the bacterial infection, suspected bacterial
infection, the fungal infection, or the suspected fungal infection
is eradicated or appears to be eradicated.
[0166] In an aspect, a disclosed method can comprise repeating the
mixing step or the administering step or both the mixing step and
the administering step for a pre-determined amount of time. In an
aspect, the pre-determined amount of time can comprise at least 5
days, at least 7 days, at least 10 days, at least 14 days, at least
21 days, at least 30 days, or more. In an aspect, the
pre-determined amount can comprise an amount of time lasting at
least 5-7 days, at least 7-10 days, at least 10-14 days, at least
14-21 days, at least 21-30 days, or at least 30 days.
[0167] In an aspect, intranasally administering can comprise
delivering to the subject the solution or suspension via the
subject's nares. In an aspect, delivering the solution or
suspension to the nares can comprise using irrigation, or using a
nasal spray, or using a metered inhaler, or using nebulization, or
using particle dispersion. In an aspect, delivering the solution or
suspension can comprise a sinus rinse, which can use positive
pressure to clean or irrigate the nasal passages and maintain the
head of the subject in an upright position. A sinus rinse delivery
device known to the art is the NeilMed.RTM. device. The art is
familiar with each of these techniques, the equipment required to
effect each of these techniques, and the means to prepare the
compounded composition for each technique of intranasal
administration.
[0168] In an aspect, a small particle nebulization delivery system
can be configured to nebulize the solution or suspension comprising
a disclosed compounded composition to produce small particles or
droplets. In an aspect, small particles or droplets can have
aerosol characteristics, wherein the particle size of the majority
(e.g., at least 50%, at least 60%, at least 70%, at least 80%, at
least 90%, or more) of the particles or droplets formed by the
nebulization can be less than about 10 microns, or less than about
8 microns, or less than about 5 microns, or less than about 3
microns. In an aspect, the particles or droplets can be about
3-about 10 microns, or about 3 microns-about 8 microns, or about 3
microns-about 5 microns, or about 5 microns-about 8 microns, or
about 5 microns-about 10 microns, or about 8 microns-about 10
microns.
[0169] In an aspect, a large particle nebulization delivery system
can be configured to nebulize the solution or suspension comprising
a disclosed compounded composition to produce large particles or
droplets. In an aspect, small particles or droplets can have
aerosol characteristics, wherein the particle size of the majority
(e.g., at least 50%, at least 60%, at least 70%, at least 80%, at
least 90%, or more) of the particles or droplets formed by the
nebulization can be more than about 10 microns, or more than about
15 microns, or more than about 20 microns, or more than about 25
microns. In an aspect, the particles or droplet can be about 10
microns - about 25 microns, or about 10 microns-about 20 microns,
or about 10 microns-about 15 microns, or about 15 microns-about 25
microns, or about 15 microns-about 20 microns, or about 20
microns-about 25 microns.
[0170] In an aspect, a disclosed method can comprise cleaning the
device.
[0171] In an aspect, a disclosed method can comprise preparing a
compounded composition. Methods of preparing a disclosed compounded
composition are discussed supra.
[0172] In an aspect, a disclosed method of treating or preventing
an infection using an intranasally administered compounded
composition can comprise modifying one or more aspect of the
disclosed method. For example, in an aspect, a method can be
modified by changing the amount of a disclosed compounded
composition intranasally administered, by changing the frequency of
the subject's use of intranasal administration, or by substituting
one disclosed compounded composition for another disclosed
compounded composition, or a combination thereof.
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