U.S. patent application number 12/319655 was filed with the patent office on 2010-04-01 for method, device, and system to control ph in pulmonary tissue of a subject.
This patent application is currently assigned to Searete LLC. Invention is credited to Roderick A. Hyde, Muriel Y. Ishikawa, Jordin T. Kare, Dennis J. Rivet, Lowell L. Wood, JR., Victoria Y.H. Wood.
Application Number | 20100081957 12/319655 |
Document ID | / |
Family ID | 42056062 |
Filed Date | 2010-04-01 |
United States Patent
Application |
20100081957 |
Kind Code |
A1 |
Hyde; Roderick A. ; et
al. |
April 1, 2010 |
Method, device, and system to control pH in pulmonary tissue of a
subject
Abstract
Methods, systems, and devices are provided which include
receiving data or providing data, wherein the data regards a
physical condition affecting one or more subjects. The data can
inform administration of a pharmaceutical composition in response
to the physical condition, wherein the pharmaceutical composition
is configured to contact pulmonary tissue to treat a pulmonary
disease or condition in the one or more subjects. The data
regarding the physical condition may be acquired prior to the
subject entering an environment where the physical condition
exists.
Inventors: |
Hyde; Roderick A.; (Redmond,
WA) ; Ishikawa; Muriel Y.; (Livermore, CA) ;
Kare; Jordin T.; (Seattle, WA) ; Rivet; Dennis
J.; (Portsmouth, VA) ; Wood, JR.; Lowell L.;
(Bellevue, WA) ; Wood; Victoria Y.H.; (Livermore,
CA) |
Correspondence
Address: |
SEARETE LLC;CLARENCE T. TEGREENE
1756 - 114TH AVE., S.E., SUITE 110
BELLEVUE
WA
98004
US
|
Assignee: |
Searete LLC,
|
Family ID: |
42056062 |
Appl. No.: |
12/319655 |
Filed: |
January 8, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12286752 |
Sep 30, 2008 |
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12319655 |
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12286729 |
Sep 30, 2008 |
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12286752 |
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12286753 |
Sep 30, 2008 |
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12286729 |
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Current U.S.
Class: |
600/532 ;
600/300; 600/538 |
Current CPC
Class: |
A61P 31/12 20180101;
A61M 11/005 20130101; A61M 15/02 20130101; A61M 11/001 20140204;
A61M 2230/208 20130101; A61M 15/0003 20140204 |
Class at
Publication: |
600/532 ;
600/300; 600/538 |
International
Class: |
A61B 5/091 20060101
A61B005/091; A61B 5/00 20060101 A61B005/00; A61B 5/08 20060101
A61B005/08 |
Claims
1.-96. (canceled)
97. A device comprising: a system including a signal-bearing medium
including one or more instructions for receiving data including
data of a physical condition affecting one or more subjects the
data informing administration of a pharmaceutical composition in
response to the physical condition, wherein the pharmaceutical
composition contacts pulmonary tissue to treat a pulmonary disease
or condition in the one or more subjects.
98. The device of claim 97, further including one or more
instructions for sensing the physical condition affecting the one
or more subjects.
99. The device of claim 97, wherein the physical condition
affecting the one or more subjects includes an environmental
condition, a signal from a global positioning device, a calendar
entry, an environmental forecast, or a weather forecast.
100. The device of claim 99, further including instructions for
receiving data of a physiological condition of the one or more
subjects.
101. The device of claim 99, wherein the calendar entry is
configured to communicate data on the environmental condition, the
environmental forecast, or the weather forecast.
102. The device of claim 100, wherein the calendar entry is
configured to communicate data on the subject's physiological
condition.
103. The device of claim 97, wherein the data of the physical
condition is acquired prior to the subject entering an environment
where the physical condition exists.
104. The device of claim 99, wherein the global positioning device
is configured to communicate data on a location of the one or more
subjects.
105. The device of claim 98, wherein a sensor located on the
subject detects the sensed physical condition.
106. The device of claim 105, wherein the sensor is located in a
sinus or nostril of the subject.
107. The device of claim 105, wherein the sensor is configured to
monitor pH of the pulmonary tissue or pH of an exhalant in the
subject.
108. The device of claim 105, wherein the sensor is configured to
monitor humidity of an exhalant, temperature, breathing rate, peak
rate of exhalation, tidal volume, vital capacity, inspiratory
capacity, expiratory reserve volume, or residual volume.
109. The device of claim 97, wherein a third party advises or
controls the administration of the pharmaceutical composition to
the one or more subjects.
110. The device of claim 97, wherein the pharmaceutical composition
includes at least one agent and is configured to achieve a selected
pH range of the pulmonary tissue of the one or more subjects.
111. The device of claim 110, wherein the at least one agent
includes at least one buffering agent.
112. The device of claim 110, wherein the at least one agent
includes at least one basic agent.
113. The device of claim 110, wherein the at least one agent
includes at least one acidic agent.
114. The device of claim 110, wherein the pharmaceutical
composition is administered as two or more distinct and
non-overlapping particle size ranges configured to contact two or
more levels of pulmonary tissue of the subject, wherein the at
least one agent is configured to achieve a selected pH range in the
two or more levels of pulmonary tissue of the subject.
115. The device of claim 114, wherein the pharmaceutical
composition includes a first agent in first-sized particles
configured to maintain a first pH range in a first level of
pulmonary tissue of the subject, and a second agent in second-sized
particles configured to maintain a second pH range in a second
level of pulmonary tissue of the subject.
116. The device of claim 97, wherein the pulmonary disease or
condition is a viral pulmonary disease or a bacterial pulmonary
disease.
117. The device of claim 97, wherein the one or more subjects are
mammalian or avian.
118. A device comprising: a system including a signal-bearing
medium including, instructions for providing data including data of
a physical condition affecting one or more subjects, the data
informing administration of a pharmaceutical composition in
response to the physical condition, wherein the pharmaceutical
composition contacts pulmonary tissue to treat a pulmonary disease
or condition in the one or more subjects.
119. The device of claim 118, further comprising instructions for
sensing the physical condition affecting the one or more
subjects.
120. The device of claim 118, wherein the physical condition
affecting the one or more subjects is an environmental condition, a
signal from a global positioning device, a calendar entry, an
environmental forecast, or a weather forecast.
121. The device of claim 120, further including instructions for
providing data of a physiological condition of the one or more
subjects.
122. The device of claim 120, wherein the calendar entry is
configured to communicate data on the environmental condition, the
environmental forecast, or the weather forecast.
123. The device of claim 121, wherein the calendar entry is
configured to communicate data on the subject's physiological
condition.
124. The device of claim 118, wherein the data of the physical
condition is acquired prior to the subject entering an environment
where the physical condition exists.
125. The device of claim 120, wherein the global positioning device
is configured to communicate data on a location of the one or more
subjects.
126. The device of claim 119, wherein a sensor located on the
subject detects the sensed physical condition.
127. The device of claim 126, wherein the sensor is located in a
sinus or nostril of the subject.
128. The device of claim 126, wherein the sensor is configured to
monitor pH of the pulmonary tissue or pH of an exhalant in the
subject.
129. The device of claim 126, wherein the sensor is configured to
monitor humidity of an exhalant, temperature, breathing rate, peak
rate of exhalation, tidal volume, vital capacity, inspiratory
capacity, expiratory reserve volume, or residual volume.
130. The device of claim 118, wherein a third party advises or
controls the administration of the pharmaceutical composition to
the one or more subjects.
131. The device of claim 118, wherein the pharmaceutical
composition includes at least one agent and is configured to
achieve a selected pH range of the pulmonary tissue of the one or
more subjects.
132. The device of claim 131, wherein the at least one agent
includes at least one buffering agent.
133. The device of claim 131, wherein the at least one agent
includes at least one basic agent.
134. The device of claim 131, wherein the at least one agent
includes at least one acidic agent.
135. The device of claim 131, wherein the pharmaceutical
composition is administered as two or more distinct and
non-overlapping particle size ranges configured to contact two or
more levels of pulmonary tissue of the subject, wherein the at
least one agent is configured to achieve a selected pH range in the
two or more levels of pulmonary tissue of the subject.
136. The device of claim 135, wherein the pharmaceutical
composition includes a first agent in first-sized particles
configured to maintain a first pH range in a first level of
pulmonary tissue of the subject, and a second agent in second-sized
particles configured to maintain a second pH range in a second
level of pulmonary tissue of the subject.
137. The device of claim 118, wherein the pulmonary disease or
condition is a viral pulmonary disease or bacterial pulmonary
disease.
138. The device of claim 118, wherein the one or more subjects are
mammalian or avian.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is related to and claims the benefit
of the earliest available effective filing date(s) from the
following listed application(s) (the "Related Applications") (e.g.,
claims earliest available priority dates for other than provisional
patent applications or claims benefits under 35 USC .sctn.119(e)
for provisional patent applications, for any and all parent,
grandparent, great-grandparent, etc. applications of the Related
Application(s)).
RELATED APPLICATIONS
[0002] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. To Be Assigned, entitled METHOD,
DEVICE, AND SYSTEM TO CONTROL PH IN PULMONARY TISSUE OF A SUBJECT,
naming Roderick A. Hyde, Muriel Y. Ishikawa, Jordin T. Kare, Dennis
J. Rivet, Lowell L. Wood, Jr. and Victoria Y. H. Wood as inventors,
filed 30 Sep. 2008, which is currently co-pending, or is an
application of which a currently co-pending application is entitled
to the benefit of the filing date. [0003] For purposes of the USPTO
extra-statutory requirements, the present application constitutes a
continuation-in-part of U.S. patent application Ser. No. To Be
Assigned, entitled METHOD, COMPOSITION, AND SYSTEM TO CONTROL PH IN
PULMONARY TISSUE OF A SUBJECT, naming Roderick A. Hyde, Muriel Y.
Ishikawa, Jordin T. Kare, Dennis J. Rivet, Lowell L. Wood, Jr. and
Victoria Y. H. Wood as inventors, filed 30 Sep. 2008, which is
currently co-pending, or is an application of which a currently
co-pending application is entitled to the benefit of the filing
date.
[0004] The United States Patent Office (USPTO) has published a
notice to the effect that the USPTO's computer programs require
that patent applicants reference both a serial number and indicate
whether an application is a continuation or continuation-in-part.
Stephen G. Kunin, Benefit of Prior-Filed Application, USPTO
Official Gazette Mar. 18, 2003, available at
http://www.uspto.gov/web/offices/com/so1/og/2003/week11/patbene.htm.
The present Applicant Entity (hereinafter "Applicant") has provided
above a specific reference to the application(s) from which
priority is being claimed as recited by statute. Applicant
understands that the statute is unambiguous in its specific
reference language and does not require either a serial number or
any characterization, such as "continuation" or
"continuation-in-part," for claiming priority to U.S. patent
applications. Notwithstanding the foregoing, Applicant understands
that the USPTO's computer programs have certain data entry
requirements, and hence Applicant is designating the present
application as a continuation-in-part of its parent applications as
set forth above, but expressly points out that such designations
are not to be construed in any way as any type of commentary and/or
admission as to whether or not the present application contains any
new matter in addition to the matter of its parent
application(s).
[0005] All subject matter of the Related Applications and of any
and all parent, grandparent, great-grandparent, etc. applications
of the Related Applications is incorporated herein by reference to
the extent such subject matter is not inconsistent herewith.
SUMMARY
[0006] Methods, systems, and devices are described herein which
include receiving data or providing data, wherein the data regards
a physical condition affecting one or more subjects. The data
regarding the physical condition may be acquired prior to the
subject entering an environment where the physical condition
exists. Methods, systems, and devices are described herein which
include receiving data including data of a physical condition
affecting one or more subjects. Methods, systems, and devices are
described herein which include providing data including data of a
physical condition affecting one or more subjects. The data can
inform administration of a pharmaceutical composition in response
to the physical condition, wherein the pharmaceutical composition
is configured to contact pulmonary tissue to treat a pulmonary
disease or condition in the one or more subjects. The methods,
systems, and devices as described herein can further include
sensing the physical condition affecting the one or more subjects.
The physical condition affecting the one or more subjects includes,
but is not limited to, an environmental condition, a signal from a
global positioning device, a calendar entry, an environmental
forecast, or a weather forecast, or a combination thereof. The
physical condition may further include a physiological condition of
the one or more subjects. A sensor may be located on the subject
which detects the sensed physical condition. The sensor may be
configured to monitor pH of the pulmonary tissue or pH of an
exhalant in the subject. The sensor may be configured to monitor
humidity of an exhalant, temperature, breathing rate, peak rate of
exhalation, tidal volume, vital capacity, inspiratory capacity,
expiratory reserve volume, or residual volume.
[0007] The pharmaceutical composition includes at least one agent,
e.g., at least one buffering agent, at least one basic agent, or at
least one acidic agent, or a combination thereof, and is configured
to achieve a selected pH range of the pulmonary tissue of the one
or more subjects. The pharmaceutical composition may be
administered as two or more distinct and non-overlapping particle
size ranges configured to contact two or more levels of pulmonary
tissue of the subject, wherein the at least one agent is configured
to achieve a selected pH range in the two or more levels of
pulmonary tissue of the subject.
[0008] Method are described herein which include receiving data
including data of a physical condition affecting one or more
subjects, the data informing administration of a pharmaceutical
composition in response to the physical condition, wherein the
pharmaceutical composition is configured to contact pulmonary
tissue to treat a pulmonary disease or condition in the one or more
subjects. The method may further include sensing the physical
condition affecting the one or more subjects. The physical
condition affecting the one or more subjects includes, but is not
limited to, an environmental condition, a signal from a global
positioning device, a calendar entry, an environmental forecast, or
a weather forecast. The method may further include receiving data
of a physiological condition of the one or more subjects. In one
aspect, the calendar entry is configured to communicate data on the
environmental condition, the environmental forecast, or the weather
forecast. In a further aspect, the calendar entry is configured to
communicate data on the subject's physiological condition. The data
of the physical condition can be acquired prior to the subject
entering an environment where the physical condition exists. The
global positioning device can be configured to communicate data on
a location of the one or more subjects. The sensor located on the
subject may detect the sensed physical condition. The sensor may be
located in a sinus or nostril of the subject. The sensor can be
configured to monitor pH of the pulmonary tissue or pH of an
exhalant in the subject. The sensor can be configured to monitor
one or more of humidity of an exhalant, temperature, breathing
rate, peak rate of exhalation, tidal volume, vital capacity,
inspiratory capacity, expiratory reserve volume, or residual
volume. In one aspect, a third party advises or controls the
administration of the pharmaceutical composition to the one or more
subjects. The method may further comprising providing data
including the data of the physical condition affecting one or more
subjects. The pharmaceutical composition may include at least one
agent and is configured to achieve a selected pH range of the
pulmonary tissue of the one or more subjects. The at least one
agent includes, but is not limited to, at least one buffering
agent, at least one agent is at least one basic agent, or at least
one agent is at least one acidic agent. The pharmaceutical
composition may be administered as two or more distinct and
non-overlapping particle size ranges configured to contact two or
more levels of pulmonary tissue of the subject, wherein the at
least one agent is configured to achieve a selected pH range in the
two or more levels of pulmonary tissue of the subject. The
pharmaceutical composition can include a first agent in first-sized
particles configured to maintain a first pH range in a first level
of pulmonary tissue of the subject, and a second agent in
second-sized particles configured to maintain a second pH range in
a second level of pulmonary tissue of the subject. The pulmonary
disease or condition includes, but is not limited to, a viral
pulmonary disease or a bacterial pulmonary disease. The one or more
subjects includes, but is not limited to, mammalian or avian.
[0009] Methods are described herein which include providing data
including data of a physical condition affecting one or more
subjects, the data informing administration of a pharmaceutical
composition in response to the physical condition, wherein the
pharmaceutical composition contacts pulmonary tissue to treat a
pulmonary disease or condition in the one or more subjects. The
method may further include sensing the physical condition affecting
the one or more subjects. The physical condition affecting the one
or more subjects includes, but is not limited to, an environmental
condition, a signal from a global positioning device, a calendar
entry, an environmental forecast, or a weather forecast. The method
may further include receiving data of a physiological condition of
the one or more subjects. In one aspect, the calendar entry is
configured to communicate data on the environmental condition, the
environmental forecast, or the weather forecast. In a further
aspect, the calendar entry is configured to communicate data on the
subject's physiological condition. The data of the physical
condition can be acquired prior to the subject entering an
environment where the physical condition exists. The global
positioning device can be configured to communicate data on a
location of the one or more subjects. The sensor located on the
subject may detect the sensed physical condition. The sensor may be
located in a sinus or nostril of the subject. The sensor can be
configured to monitor pH of the pulmonary tissue or pH of an
exhalant in the subject. The sensor can be configured to monitor
one or more of humidity of an exhalant, temperature, breathing
rate, peak rate of exhalation, tidal volume, vital capacity,
inspiratory capacity, expiratory reserve volume, or residual
volume. In one aspect, a third party advises or controls the
administration of the pharmaceutical composition to the one or more
subjects. The method may further comprising receiving data
including the data of the physical condition affecting one or more
subjects. The pharmaceutical composition may include at least one
agent and is configured to achieve a selected pH range of the
pulmonary tissue of the one or more subjects. The at least one
agent includes, but is not limited to, at least one buffering
agent, at least one agent is at least one basic agent, or at least
one agent is at least one acidic agent. The pharmaceutical
composition may be administered as two or more distinct and
non-overlapping particle size ranges configured to contact two or
more levels of pulmonary tissue of the subject, wherein the at
least one agent is configured to achieve a selected pH range in the
two or more levels of pulmonary tissue of the subject. The
pharmaceutical composition can include a first agent in first-sized
particles configured to maintain a first pH range in a first level
of pulmonary tissue of the subject, and a second agent in
second-sized particles configured to maintain a second pH range in
a second level of pulmonary tissue of the subject. The pulmonary
disease or condition includes, but is not limited to, a viral
pulmonary disease or a bacterial pulmonary disease. The one or more
subjects includes, but is not limited to, mammalian or avian.
[0010] Systems are described herein which include a signal-bearing
medium including one or more instructions for receiving data
including data of a physical condition affecting one or more
subjects, the data informing administration of a pharmaceutical
composition in response to the physical condition, wherein the
pharmaceutical composition contacts pulmonary tissue to treat a
pulmonary disease or condition in the one or more subjects. The
system may further include one or more instructions for sensing the
physical condition affecting the one or more subjects. The, system
may further include instructions for receiving data of a
physiological condition of the one or more subjects.
[0011] Systems are described herein which include circuitry for
receiving data including data of a physical condition affecting one
or more subjects, the data informing administration of a
pharmaceutical composition in response to the physical condition,
wherein the pharmaceutical composition contacts pulmonary tissue to
treat a pulmonary disease or condition in the one or more subjects.
The system may further include circuitry for sensing the physical
condition affecting the one or more subjects.
[0012] Systems are described herein which include a signal-bearing
medium including instructions for providing data including data of
a physical condition affecting one or more subjects, the data
informing administration of a pharmaceutical composition in
response to the physical condition, wherein the pharmaceutical
composition contacts pulmonary tissue to treat a pulmonary disease
or condition in the one or more subjects. Systems are described
herein which include circuitry for providing data including data of
a physical condition affecting one or more subjects, the data
informing administration of a pharmaceutical composition in
response to the physical condition, wherein the pharmaceutical
composition contacts pulmonary tissue to treat a pulmonary disease
or condition in the one or more subjects. The system may further
include instructions for sensing the physical condition affecting
the one or more subjects.
[0013] Systems are described herein which include circuitry for
providing data including data of a physical condition affecting one
or more subjects, the data informing administration of a
pharmaceutical composition in response to the physical condition,
wherein the pharmaceutical composition contacts pulmonary tissue to
treat a pulmonary disease or condition in the one or more subjects.
The system may further include circuitry for sensing the physical
condition affecting the one or more subjects.
[0014] Devices are described herein which include systems including
a signal-bearing medium including one or more instructions for
receiving data including data of a physical condition affecting one
or more subjects, the data informing administration of a
pharmaceutical composition in response to the physical condition,
wherein the pharmaceutical composition contacts pulmonary tissue to
treat a pulmonary disease or condition in the one or more subjects.
The device may further include one or more instructions for sensing
the physical condition affecting the one or more subjects. The
device may further include instructions for receiving data of a
physiological condition of the one or more subjects.
[0015] Devices are described herein which include systems including
a signal-bearing medium including one or more instructions for
providing data including data of a physical condition affecting one
or more subjects, the data informing administration of a
pharmaceutical composition in response to the physical condition,
wherein the pharmaceutical composition contacts pulmonary tissue to
treat a pulmonary disease or condition in the one or more subjects.
The device may further include one or more instructions for sensing
the physical condition affecting the one or more subjects. The
device may further include instructions for providing data of a
physiological condition of the one or more subjects.
[0016] The foregoing summary is illustrative only and is not
intended to be in any way limiting. In addition to the illustrative
aspects, embodiments, and features described above, further
aspects, embodiments, and features will become apparent by
reference to the drawings and the following detailed
description.
BRIEF DESCRIPTION OF THE FIGURES
[0017] FIGS. 1A and 1B depict a diagrammatic view of one aspect of
an exemplary embodiment of a method, device, or system that may
serve as an illustrative environment for subject matter
technologies.
[0018] FIGS. 2A, 2B, and 2C depict a diagrammatic view of one
aspect of an exemplary embodiment of a method, device, or system
that may serve as an illustrative environment for subject matter
technologies.
[0019] FIGS. 3A and 3B depict a logic flowchart of a method such as
those depicted in FIGS. 1 and 2.
[0020] FIG. 4 depicts a logic flowchart of a method such as those
depicted in FIGS. 1 and 2.
[0021] FIG. 5 depicts a logic flowchart of a device such as those
depicted in FIGS. 1 and 2.
[0022] FIGS. 6A, 6B, and 6C depicts a logic flowchart of a method
such as those depicted in FIGS. 1 and 2.
[0023] FIG. 7 depicts a logic flowchart of a device such as those
depicted in FIGS. 1 and 2.
[0024] FIGS. 8A, 8B, 8C, and 8D depicts a logic flowchart of a
method such as those depicted in FIGS. 1 and 2.
DETAILED DESCRIPTION
[0025] In the following detailed description, reference is made to
the accompanying drawings, which form a part hereof. In the
drawings, similar symbols typically identify similar components,
unless context dictates otherwise. The illustrative embodiments
described in the detailed description, drawings, and claims are not
meant to be limiting. Other embodiments may be utilized, and other
changes may be made, without departing from the spirit or scope of
the subject matter presented here.
[0026] The present application uses formal outline headings for
clarity of presentation. However, it is to be understood that the
outline headings are for presentation purposes, and that different
types of subject matter may be discussed throughout the application
(e.g., method(s) may be described under composition heading(s)
and/or kit headings; and/or descriptions of single topics may span
two or more topic headings). Hence, the use of the formal outline
headings is not intended to be in any way limiting.
[0027] Methods, systems, and devices are described herein which
include receiving data or providing data, wherein the data regards
a physical condition affecting one or more subjects. The data
regarding the physical condition may be acquired prior to the
subject entering an environment where the physical condition
exists. Methods, systems, and devices are described herein which
include receiving data including data of a physical condition
affecting one or more subjects. Methods, systems, and devices are
described herein which include providing data including data of a
physical condition affecting one or more subjects. The data can
inform administration of a pharmaceutical composition in response
to the physical condition, wherein the pharmaceutical composition
is configured to contact pulmonary tissue to treat a pulmonary
disease or condition in the one or more subjects. The methods,
systems, and devices as described herein can further include
sensing the physical condition affecting the one or more subjects.
The physical condition affecting the one or more subjects includes,
but is not limited to, an environmental condition, a signal from a
global positioning device, a calendar entry, an environmental
forecast, or a weather forecast, or a combination thereof. The
physical condition may further include a physiological condition of
the one or more subjects. A sensor may be located on the subject
which detects the sensed physical condition. The sensor may be
configured to monitor pH of the pulmonary tissue or pH of an
exhalant in the subject. The sensor may be configured to monitor
humidity of an exhalant, temperature, breathing rate, peak rate of
exhalation, tidal volume, vital capacity, inspiratory capacity,
expiratory reserve volume, or residual volume.
[0028] The pharmaceutical composition includes at least one agent,
e.g., at least one buffering agent, at least one basic agent, or at
least one acidic agent, or a combination thereof, and is configured
to achieve a selected pH range of the pulmonary tissue of the one
or more subjects. The pharmaceutical composition may be
administered as two or more distinct and non-overlapping particle
size ranges configured to contact two or more levels of pulmonary
tissue of the subject, wherein the at least one agent is configured
to achieve a selected pH range in the two or more levels of
pulmonary tissue of the subject.
[0029] With reference to the figures, and with reference now to
FIGS. 1 through 8, depicted is one aspect of a system that may
serve as an illustrative environment of and/or for subject matter
technologies, for example, a method comprising receiving data
including data of a physical condition affecting one or more
subjects, the data informing administration of a pharmaceutical
composition in response to the physical condition, wherein the
pharmaceutical composition is configured to contact pulmonary
tissue to treat a pulmonary disease or condition in the one or more
subjects; or a method for treating a pulmonary viral infectious
disease in a subject comprising administering a pharmaceutical
composition including at least one agent to a pulmonary tissue of
the subject, wherein the pharmaceutical composition is administered
as two or more distinct and non-overlapping particle size ranges
configured to contact two or more levels of pulmonary tissue of the
subject, wherein the at least one agent is configured to achieve a
selected pH range in the two or more levels of pulmonary tissue of
the subject; or a device comprising an aerosol generator and a
pharmaceutical composition including a membrane selective for a
charged ion configured to achieve a selected pH of a pulmonary
tissue in a subject. Accordingly, the present application first
describes certain specific exemplary methods of FIGS. 1 through 8;
thereafter, the present application illustrates certain specific
exemplary methods. Those having skill in the art will appreciate
that the specific methods described herein are intended as merely
illustrative of their more general counterparts.
[0030] Continuing to refer to FIG. 1, depicted is a partial
diagrammatic view of an illustrative embodiment of a method for
treating a pulmonary viral infectious disease in a subject or a
device 110 for use with the method. In FIG. 1A, a method for
treating a pulmonary viral infectious disease in a subject 100
includes administering a pharmaceutical composition 120 including
at least one agent 130, 140 to a pulmonary tissue of the subject,
wherein the pharmaceutical composition is administered as two or
more distinct and non-overlapping particle size ranges 130, 140
configured to contact two or more levels 160, 170 of pulmonary
tissue 150 of the subject, In FIG. 1B, the method includes
administering a pharmaceutical composition 120 including at least
one agent 130, 140 to a pulmonary tissue 150 of the subject,
wherein the pharmaceutical composition is administered as two or
more distinct and non-overlapping particle size ranges 130, 140,
wherein the at least one agent is configured to achieve a selected
pH range in the two or more levels 160, 170 of pulmonary tissue 150
of the subject. The two or more distinct and non-overlapping
particle size ranges 130, 140, may be configured to achieve a
selected pH range in the two or more levels, for example, in the
bronchus or bronchi 160 of the lungs, or further into the bronchial
tree 170 towards the bronchi, bronchioles, alveolar duct, or
alveoli of the lungs of the subject.
[0031] Continuing to refer to FIG. 2, FIG. 2A depicts a partial
diagrammatic view of an illustrative embodiment of a method
comprising receiving data 260 including data 270 of a physical
condition affecting one or more subjects 200, the data 270
informing administration 215 of a pharmaceutical composition 220,
230, 240 in response to the physical condition, wherein the
pharmaceutical composition is configured to contact pulmonary
tissue 250, 280, 290 to treat a pulmonary disease or condition in
the one or more subjects 200. The system or method may include a
device 210. The system or method includes providing data 270
including data of a physical condition affecting one or more
subjects, the data informing administration 215 of a pharmaceutical
composition in response to the physical condition, wherein the
pharmaceutical composition 220, 230, 240 contacts pulmonary tissue
250 to treat a pulmonary disease or condition in the one or more
subjects. In FIGS. 2B and 2C, the pharmaceutical composition 220
includes at least one agent 230, 240 and is configured to achieve a
selected pH range 280, 290 of the pulmonary tissue 250 of the one
or more subjects 200. Two or more distinct and non-overlapping
particle size ranges 230, 240, may be configured to achieve a
selected pH range in the two or more levels, for example, in the
bronchus or bronchi 280 of the lungs, or further into the bronchial
tree 290 towards the bronchi, bronchioles, alveolar duct, or
alveoli of the lungs of the subject.
[0032] FIGS. 3A and 3B depict a logic flowchart of a method such as
those depicted in FIGS. 1 and 2. FIGS. 3A and 3B illustrate an
exemplary method 300 for receiving data including data of a
physical condition affecting one or more subjects, the data
informing administration of a pharmaceutical composition in
response to the physical condition, wherein the pharmaceutical
composition is configured to contact pulmonary tissue to treat a
pulmonary disease or condition in the one or more subjects.
[0033] FIG. 4 depicts a logic flowchart of a method such as those
depicted in FIGS. 1 and 2. FIG. 4 illustrates an exemplary method
400 including providing data including data of a physical condition
affecting one or more subjects, the data informing administration
of a pharmaceutical composition in response to the physical
condition, wherein the pharmaceutical composition contacts
pulmonary tissue to treat a pulmonary disease or condition in the
one or more subjects.
[0034] FIG. 5 depicts a logic flowchart of a device such as those
depicted in FIGS. 1 and 2. FIG. 5 illustrates an exemplary device
500 including a signal-bearing medium which includes one or more
instructions for receiving data including data of a physical
condition affecting one or more subjects the data informing
administration of a pharmaceutical composition in response to the
physical condition, wherein the pharmaceutical composition contacts
pulmonary tissue to treat a pulmonary disease or condition in the
one or more subjects.
[0035] FIGS. 6A, 6B, and 6C depict a logic flowchart of a method
such as those depicted in FIGS. 1 and 2. FIGS. 6A, 6B, and 6C
illustrate an exemplary method 600 for treating a pulmonary viral
infectious disease in a subject which includes administering a
pharmaceutical composition including at least one charged ion to a
pulmonary tissue of the subject, wherein the pharmaceutical
composition includes a membrane selective for the charged ion and
is configured to achieve a selected pH of the pulmonary tissue in
the subject.
[0036] FIG. 7 depicts a logic flowchart of a device such as those
depicted in FIGS. 1 and 2. FIG. 7 illustrates an exemplary device
700 including an aerosol generator, and a pharmaceutical
composition including a membrane selective for a charged ion
configured to achieve a selected pH of a pulmonary tissue in a
subject.
[0037] FIGS. 8A, 8B, 8C, and 8D depict a logic flowchart of a
method such as those depicted in FIGS. 1 and 2. FIGS. 8A, 8B, 8C,
and 8D illustrate an exemplary method 800 for treating a pulmonary
viral infectious disease in a subject which includes administering
a pharmaceutical composition including at least one agent to a
pulmonary tissue of the subject, wherein the pharmaceutical
composition is administered as two or more distinct and
non-overlapping particle size ranges configured to contact two or
more levels of pulmonary tissue of the subject, wherein the at
least one agent is configured to achieve a selected pH range in the
two or more levels of pulmonary tissue of the subject.
Types of Data Regarding a Physical Condition or Environmental
Condition
[0038] A method, system, or device is provided for receiving data
including data of a physical condition affecting one or more
subjects. The method, system, or device may sense one or more
physical condition that is one or more environmental condition,
signal from a global positioning device, calendar entry,
environmental forecast, or weather forecast. An environmental
condition may include, but is not limited to, air quality
associated with smog, forest fire, volcanic ash; allergen
conditions such as pollen count, mold spores, dander; weather
conditions such as temperature, pressure, wind speed and humidity;
and infection risk conditions.
[0039] The method, system, or device may further include a global
positioning device to sense the current location of one or more
subjects relative to the environmental condition. A calendar entry
may be used to sense a current or future location of one or more
subjects relative to the environmental condition. The calendar
provides the date and time as well as scheduling information
specific to a given subject or group of subjects regarding planned
activities and or outings in the near and far future. An
environmental forecast and or a weather forecast in combination
with a calendar entry may predict a future environmental condition
of one or more subjects. One or more subjects may communicate,
provide, or receive information regarding current and future
physical conditions for a given location and time. This information
may be used to alert one or more subjects that they are currently
in or will be entering in the future an environment with conditions
that may increase the risk of contracting an infectious agent. In
response to this information, one or more subjects may choose to
self-administer a pharmaceutical composition that may prevent or
mitigate the infection. Alternatively, the device may automatically
deliver a pharmaceutical composition to one or more subjects based
on the information regarding environmental conditions, location and
time.
[0040] A number of environmental conditions associated with poor
air quality may affect lung function or susceptibility to disease.
For example, gases, particulates, and other chemicals associated
with smog, forest fires and volcanic ash may contribute to poor air
quality in a given location at a given time. As such information
regarding current and projected environmental conditions related to
air quality may be measured in a current location and or a future
location and used to guide treatment of the lungs with the
pharmaceutical composition.
[0041] The effects of smog on lung function and susceptibility to
disease vary according to factors such as age, state of health,
time of exposure, and dosage, but general symptoms include
coughing, sneezing, headaches, tiredness, irritation, nausea, and
hoarseness of the throat, nose, and eyes, and constrictions of the
chest. In addition, nitrogen dioxide and ground-level ozone
associated with smog may cause reductions in the immune system's
ability to fight viruses and bacteria in the respiratory system
(see, e.g., Chauhan & Johnston BMB 68:95-112, 2003;
Hollingsworth, et al., Proc. Am. Thorac. Soc. 4:240-246, 2007,
which are incorporated herein by reference). In one aspect,
exposure to nitrogen dioxide and ozone increases expression of
intracellular adhesion molecule 1 (ICAM-1), an epithelial cell
receptor for human rhinovirus. The gaseous and particulate
components of smog may also damage the pulmonary epithelium.
Nitrogen dioxide and ground-level ozone as well as sulfur dioxide
may cause damage to the mucociliary clearance system or ciliary
dyskinesis. The mucociliary clearance system plays a pivotal role
in the protection of the respiratory tract against inhaled noxious
agents such as airborne allergens, bacteria or viruses by trapping
the agents in mucus and transporting the agents towards the pharynx
and out of the lung by ciliary beating or coughing. As a result,
the lung's ability to resist disease is reduced, and illnesses,
such as asthma, bronchitis and emphysema, may be aggravated.
[0042] Gases associated with smog including sulfur dioxide, ozone,
nitrogen dioxide, total reduce sulfur compounds, and carbon
monoxide may be measured using a number of methods, e.g., passive
sampling methods, active sampling methods, automatic methods and
remote methods. Passive sampling methods provide reliable,
cost-effective air quality analysis and may provide a good
indication of average pollution concentrations over a period of
weeks or months. Passive samplers do not involve any pumping of air
but instead rely on the natural flow of ambient air past the open
end of a diffusion tube which contains two stainless steel gauzes
placed at one end of a short cylinder. In the case of a nitrogen
dioxide sampler, the steel gauze contains a coating of
triethanolamine, which converts the nitrogen dioxide in the air to
nitrite, the latter of which is trapped within the steel gauze and
can be measured by laboratory analysis. Active sampling methods use
physical or chemical methods to collect polluted air, and analysis
is carried out later in the laboratory. Typically, a known volume
of air is pumped through a collector, such as a filter or a
chemical solution, for a set period of time. The collector is later
removed for analysis. Samples can be collected daily, providing
measurements for short time periods. Automatic methods produce
high-resolution measurements of hourly pollutant concentrations or
better, at a single point as measured using a variety of methods
including spectroscopy and gas chromatography. Remote optical/long
path-analyzers use spectroscopic techniques to make real-time
measurements of the concentrations of a range of pollutants
including nitrogen dioxide and sulfur dioxide. In one aspect,
hydroperoxyl radical, one of the most abundant free radicals in the
atmosphere, may be measured using a chemiluminescence detection
system as in U.S. Pat. No. 7,285,243, which is incorporated herein
by reference.
[0043] In addition to noxious gases, smog may also contain
particulate matter, e.g., black carbon. Black carbon is derived
primarily from diesel exhaust and wood burning. These particles are
small enough to penetrate and irritate the human pulmonary system.
Black carbon is also able to adsorb other species such as air
toxins. Black carbon may be measured using an air monitoring
systems such as, for example, the Aethalometer.TM. (from, e.g.,
Magee Scientific, Inc. Berkeley, Calif.). The Aethalometer.TM. is a
tape sampler that takes in air at a controlled rate and passes the
air though a glass fiber filter. As the particulate matter
accumulates on the filter, the device measures the attenuation of
light at two channels. The black carbon channel is recorded at 880
nm and the UV channel is at 370 nm. Other devices for measuring air
borne particulate matter include the nephelometer and the tapered
element oscillating microbalance (TEOM).
[0044] Forest fires and other vegetation fires generate smoke which
contributes to air pollution and may consequently alter pulmonary
function in a subject. Vegetative fire smoke consists primarily of
water vapor, volatile organic compounds, semi-volatile organic
compounds, particulate matter, and permanent gases. The gases found
in forest fire smoke include CO, CO.sub.2, NO.sub.2, and ozone,
similar to the contaminants associated with air pollution. Air
quality monitoring may be done to intermittently or continuously
measure key components of forest fire smoke. Air quality monitoring
of CO, CO.sub.2, and other permanent gases as well as particulates
may be accomplished in the field using portable instruments. These
may be hand-held, backpack, and or luggage carried; mobile labs or
roving systems; and wearable instruments. For example,
miniaturization of an ion mobility spectrometry system either
"worn" or as part of a uniform, for example, may be used as an
alarm device as well as for monitoring human exposure. Hand-held
sensors may be used to measure CO, CO.sub.2 and other permanent
gases as well as particulate matter. Portable versions of
photoionizing devices, gas chromatography-mass spectrometry, gas
chromatography-ion mobility spectrometry, gas chromatography-gas
chromatography, and ion mobility spectrometers may be used for
monitoring volatile organic compounds. Depending upon distance from
the flame front, the instruments may be defined as stand-off and
point devices (near the flame front). The instruments may be
defined as active or passive depending upon whether or not the
sample is excited or not. And depending upon the height-level of
the monitoring, the field methods can be classified as
ground-based, aerial or space (see, e.g., Statheropoulos &
Goldammer, "Vegetation Fire Smoke: Nature, Impacts and Policies to
Reduce Negative Influences on Humans and the Environment" presented
at 4.sup.th International Wildland Fire Conference, Sevilla, Spain,
May 13-17, 2007).
[0045] A volcanic eruption emits ash and gases into the atmosphere
that can effect pulmonary function. The potential respiratory
symptoms in the subject from inhalation of volcanic ash include but
are not limited to nasal irritation and discharge, throat
irritation and sore throat, sometimes accompanied by dry coughing,
severe bronchitic symptoms (hacking cough, production of sputum,
wheezing, or shortness of breath) in individuals with pre-existing
respiratory complaints, and airway irritation including shortness
of breath, wheezing, and coughing in individuals with asthma or
bronchitis. The severity of symptoms depends on a number of
factors, including airborne concentration of total suspended
particles, proportion of respirable particles in the ash (less than
10 .mu.m), frequency and duration of exposure, presence of free
crystalline silica and volcanic gases or aerosols mixed with the
ash, meteorological conditions, and host factors (existing health
conditions and the propensity of those exposed to incur respiratory
problems), and the use of respiratory protective equipment. In
addition, volcanic eruptions are the largest source of naturally
occurring sulfur dioxide in the atmosphere.
[0046] Data from weather satellites may be used to identify
volcanic plumes and to track their movement downwind. Explosive
eruptions inject enormous volumes of volcanic ash and gases into
the atmosphere, where the ash is carried downwind hundreds or
thousands of miles and often remains airborne for days to weeks. As
the ash and gas move and disperse downwind, it becomes increasingly
difficult to distinguish an eruption cloud visually from weather
clouds, especially at night or in poor weather. Sensors aboard
geostationary and polar orbiting weather satellites record the
amount of thermal energy in several different wavelengths emitted
from weather and eruption clouds and the Earth's surface. The image
data from these different wavelengths may be used to detect and
track an eruption cloud. Sulfur dioxide associated with volcanic
eruptions may be measured from space using a satellite equipped
with a total ozone mapping spectrometer.
[0047] An environmental condition may also include allergen
conditions, e.g., pollen count, mold spores, and dander. Allergens
such as pollen, mold, and dander may be another source of pulmonary
irritation. In general, pollen are found mainly in the coarse
fraction of airborne particles. Pollen in a given location may be
measured by passing the ambient air through a filter which captures
particulate matter, including pollen. The trapped pollen may be
identified and quantified by counting the pollen spores under an
optical microscope. Alternatively, pollen floating in air may be
counted in real time using a pollen sensor that includes, for
example, a light beam and a receiver for measuring the intensity of
a light beam scattered by floating particles in a detection zone
and a second receiver for measuring the intensity of a polarized
light beam in a direction perpendicular to light illuminated by the
light beam and means for measuring the degree of polarization of
the particles for distinguishing pollen particles from other
particles (U.S. Pat. No. 7,119,900, which is incorporated herein by
reference).
[0048] In some aspects, allergen conditions may be inferred from
the time of year in a given location. For example, the presence of
pollen or other allergen may be inferred from the time of year in a
given location. Pollen season begins earlier in warmer climates
than in cooler climates and typically ends after the first hard
freeze. Trees generally pollinate first followed by grasses and
weeds. The time period over which a given pollen type is likely to
be present may be dependent upon the geographical location. In one
aspect, along the Northwest United States coast, the tree pollen
season lasts from February to June, the grasses pollen season lasts
from May to August, and the weeds pollen season lasts from May to
September. In contrast, in the arid Southwest United States the
tree pollen season lasts from February to June, the grasses pollen
season lasts from April to October, and the weeds pollen season
lasts from February to October.
[0049] Seasonal weather patterns influence the amount of pollen
that plants produce in a growing season. In addition, daily weather
conditions also have an effect on the amount of aggravating
wind-dispersed pollens in the air. Blustery, windy days stir up
pollen whereas windless and rainy days may have lower pollen
counts. Data regarding probable pollen in the atmosphere at a given
time of year may be combined with data regarding the temperature,
humidity and wind on a given day in a given location.
[0050] Other allergens such as mold spores as well as dander,
including house mite, cockroach, cat, or dog allergens may also be
found in the coarse fraction of airborne particles. Airborne mold
spores may be measured by passing the ambient air through a filter
which captures the mold spores. Material trapped by the filter may
be examined by optical microscopy. In some aspects, the filter
itself may be washed or dissolved in a sterile aqueous solution and
mold released into the solution may be cultured on an agar plate or
in a liquid broth to identify which if any mold strains are in the
sampled air.
[0051] An environmental condition may also include weather
conditions, e.g., temperature, humidity, wind speed, and air
pressure. A number of weather related physical conditions that may
affect lung function or susceptibility to disease may be measured
including but not limited to temperature and humidity. Temperature
may be simply measured using a thermometer. Humidity is normally
measured as relative humidity and may be measured using a
hygrometer. Temperature and humidity are closely linked. Relative
humidity is the percentage of moisture in the air relative to the
maximum amount the air can hold at a given temperature. When air at
a given temperature contains all the water vapor it can hold at
that temperature, it has a relative humidity of 100 percent. If the
humidity exceeds 100 percent, moisture will begin to condense from
the air. Warm air can hold more moisture than cool air, so that the
relative humidity of a sample of air will change as the temperature
changes, even though the actual amount of moisture in the sample
air does not. As a sample of air cools the relative humidity
rises.
[0052] The condition of a potentially infectious environment may be
directly measured by assessing the presence or absence of air borne
pathogens. Airborne pathogens, e.g., viral particles, may be
detected by recovering the particles in or on a collection medium
(liquid, semisolid, or solid substrate), and then assaying the
substrate for the presence of the targeted virus using an
appropriate assay system. Airborne viral articles may be collected
using an impinger in which a converged stream of environmental air
is directed onto a liquid collection medium (see, e.g., Hermann, et
al., Appl. Environ. Microbiol. 72:4811-4818, 2006, which is
incorporated herein by reference). Other capture mediums include,
but are not limited to, filters, bubblers, or impactors. Real time
polymerase chain reaction (RT-PCR) amplification may be used to
detect and identify viral pathogens. Methods are provided for using
RT-PCR to detect and identify the avian H5N1 influenza virus (Chen
et al., J. Med. Microbiol. 56:603-607, 2007, which is incorporated
herein by reference). Similarly, airborne rhinovirus may be
collected on Teflon membranes and identified and quantified by PCR
(see, e.g., Myatt, et al., BMC Public Health 3:5, 2003, which is
incorporated herein by reference). Alternatively, airborne
pathogens may be detected using some form of microsensor. For
example, arrays of silicon cantilever beams as microresonator
sensors are provided to detect individual virus particles (see,
e.g., Gupta, et al., Applied Physics Lett. 84: 1976-1978, 2003,
which is incorporated herein by reference).
[0053] Alternatively, an infection risk condition may be implied
from the time of year and global location. For example, "flu"
season or that portion of the year in which there are regular
outbreaks of influenza infections usually occurs in the cold half
of the year in each hemisphere. In the United States, flu season
may run from November through March of the following year. During
the colder portion of the year, people remain indoors more often
and as such are in closer contact, allowing for easier viral
transmission. In addition, cold temperatures lead to drier air and
may dehydrate mucus and as such prevent the body from effectively
expelling virus particles. The virus itself may survive longer on
surfaces in cold temperatures.
[0054] Alternatively, an infection risk condition may be
communicated to a subject or group of subjects from an agency
tracking viral infection in a given location. Such an agency might
be, for example, a local Public Health authority, the Center for
Disease Control (CDC), the World Health Organization (WHO) or
similar agencies in a given location. The location may be the
current location of the subject or group of subjects.
Alternatively, the location may be the location to which the
subject or group of subjects will be traveling to in the near
future. The CDC provides weekly influenza surveillance data broken
down by region such as Northeast versus Pacific.
[0055] Data regarding environmental conditions may be communicated,
provided, or received from any of a number of sensors including but
not limited to sensors implanted in a subject or group of subjects,
sensors carried or worn by a subject or group of subjects, sensors
present in a room(s) and or building(s) frequented by a subject or
group of subjects, public spaces frequented by a subject or group
of subjects, remote sensors in distance locations and or associated
with satellites, or combinations thereof. Information communicated,
provided, or received from the sensors is communicated to a subject
or group of subjects.
[0056] Data regarding environmental conditions may be collected by
a sensor that is incorporated into the subject. For example, a
miniaturized sensor may be implanted or inserted into a part of the
respiratory tract such as, for example, a nostril, a sinus, a
tooth, back of the throat, or other part of the respiratory system
over which air normally flows. Alternatively, the miniaturized
sensor may be implanted or inserted on other parts of the body.
Device may include a micromechanical sensor that enables
measurement of pressure, a temperature, an air mass, an air
quality, a dew point, a humidity of a gas, a chemical composition
of a gas or of a liquid, for example (see, e.g., U.S. Pat. No.
7,213,465, which is incorporated herein by reference).
[0057] Data regarding environmental conditions may be communicated,
provided, or received from a sensor that is carried by the subject
or group of subjects. For example, the sensor may be incorporated
into everyday devices normally carried by a subject or group of
subjects. Examples include but are not limited to a cell phone, a
pager, a PDA, blackberry, or other. For example, Sakhpara describes
a mobile telecommunications handset with an air pollution meter
(U.S. Patent Application 2008/0045156 A1, which is incorporated
herein by reference). Alternatively, the device may be worn by the
subject. Examples include, but are not limited to, a sensor device
worn directly over the mouth and or nose, a sensor device worn on
the back or around the waist or neck, a sensor device incorporated
into a piece of jewelry such as a necklace, bracelet, wrist watch,
and the like, or a sensor device incorporated into an article of
clothing.
[0058] Data regarding environmental conditions may be communicated,
provided, or received from a sensor that is situated in a private
or public room or building or open space frequented by a subject or
group of subjects such as, for example, a home, office, classroom,
shopping mall, or other public space. The sensor may be
incorporated into a stand alone device that sits on a desk, is
mounted on the wall, or stands on the floor. Alternatively, the
sensor may be incorporated into an air flow system associated with
a room or building or public space. A sub-assembly device is
provided for detecting and reporting on allergen data within a room
or building in which the device is located (U.S. Pat. No. RE39,871,
which is incorporated herein by reference. Information from the
sensor may be sent wirelessly to the subject or group of
subjects.
[0059] Data regarding environmental conditions may be communicated,
provided, or received from a remote sensor and sent either directly
or indirectly to a subject of group of subjects. For example,
information regarding an environmental condition such as air
quality, for example, may be received wirelessly by a subject or
group of subjects from one or more mobile measuring units with
global positioning information (see, e.g., U.S. Patent Application
2008/0024323 A1, which is incorporated herein by reference).
Alternatively, information regarding environmental and/or weather
conditions may be communicated, provided, or received indirectly
from any of a number of collecting agencies. Agencies which collect
information regarding environmental conditions include, but are not
limited, to, local, national and or international weather services,
e.g., the National Oceanic and Atmospheric Administration (NOAA)
and the National Weather Service; local, national and or
international fire monitoring agencies such as, for example, the
United States Forest Service (USFS) and Global Forest Information
Service (GFIS); local, national and or international volcano
monitoring agencies such as, for example, United States Geological
Survey (USGS). Information regarding weather conditions and air
quality may be provided by a service that accumulates such
information for one or more locations and transmits the information
to a subject or group of subjects to a device such as a computer, a
PDA, a cellular telephone, a pager, a dedicated display device or a
public display (U.S. Pat. No. 7,181,345, which is incorporated
herein by reference). Other sources of information include, but are
not limited to, the internet, television and radio stations, public
health departments, allergy clinics, and the like.
Type of Data Regarding a Physical Condition--Physiological
Condition
[0060] A method, system, or device is provided for receiving data
including data of a physical condition affecting one or more
subjects. The method, system, or device may further sense one or
more physical conditions which include one or more physiological
condition of a subject or group of subjects. The physiological
condition may be the pH of the pulmonary tissue of a subject or
group of subjects. The physiological condition may further be one
or more of the humidity of exhalant, temperature, breathing rate,
peak rate of exhalation, tidal volume, vital capacity, inspiratory
capacity, expiratory reserve volume, or residual volume of a
subject or group of subjects.
[0061] The method, system, or device includes one or more sensors
configured to monitor at least one of pH of the pulmonary tissue in
the subject or pH of an exhalant in the subject. The one or more
monitoring sensor may be part of a hand held device. The one or
more sensor may be associated with a mask worn over the mouth and
or nose of the subject. In some aspects, the one or more monitoring
sensor may be miniaturized and temporarily or permanently
incorporated into an airway passage of the subject. The one or more
monitoring sensor may be incorporated into the upper respiratory
tract, including, but are not limited to, the nasal cavity, pharynx
and or larynx. Data generated by the one or more monitoring sensor
may be sent wirelessly to a device associated with the subject and
or to a device associated with a third party, e.g., a physician or
other caregiver.
[0062] The pH of pulmonary tissue in a subject may be measured in
exhaled breath of the subject. For example, pH may be monitored in
expired breath condensate (EBC). EBC consists of: (1) aerosolized
particles of airway lining fluid evolved from the airway wall by
turbulent airflow, that serves as seeds for substantial; and (2)
water vapor condensation, which then serves to trap (3) water
soluble volatile gases. The normal range of pH values of fluid
lining human airways ranges from pH 6.5 to pH 7.5 (see, e.g.,
Tanaka, et al., Eur. Respir. J. 11:1301-1306, 1998, which is
incorporated herein by reference). Sampling may be accomplished by
having a subject breath at tidal volumes orally into a mouthpiece
attached to a cold condenser (RTube, Respiratory Research Inc.,
Austin, Tex.; ECoScreen II, VIASYS Healthcare, Yorba Linda,
Calif.). In this instance, pH may be assayed after Argon deaeration
of the EBC. In addition to oral collection methods, EBC may be
collected through a nasal cannula and or an endotracheal tube.
Collection times may be as short as 90 seconds or over an hour to
obtain sufficient EBC. Ten minutes of breathing is commonly
employed. Alternatively, pulmonary pH of a subject may be monitored
in real time using a miniaturized self-condensing pH sensor as
described by Tsukashima, et al., in U.S. Patent Application
2007/0068810 A1, which is incorporated herein by reference.
[0063] In some instances, the pH of expired breath condensate (EBC)
may be monitored by a micro-sensor using a pH sensitive
ion-sensitive effect transistor (ISFET). In this instance, a metal
oxide such as SiO.sub.2, Ta.sub.2O.sub.5, and or Al.sub.2O.sub.3,
for example, may donate or accept a proton from the solution (in
this instance the breath condensate) and leave a negatively charged
or a positively charged surface group, respectively, thus
generating a surface potential that varies depending upon the pH of
the solution (see, e.g., U.S. Pat. Nos. 6,132,893 and 6,464,940,
which are incorporated herein by reference).
[0064] The sensor as provided in the method, system, or device for
monitoring the pH in the expired breath condensate of the subject
may be sufficiently small to be semi-permanently or permanently
located in a segment of the airway of a subject. The sensor may be
incorporated into the upper respiratory tract, including, but not
limited to, the nasal cavity, pharynx and or larynx. Alternatively,
the sensor may be incorporated into a dental or nasal prosthesis
(see, e.g., U.S. Patent Application 2007/0106138 A1, which is
incorporated herein by reference) or into a piece of jewelry such
as, for example, a nose or tongue piercing (see, e.g., U.S. Patent
Application 2005/0209526 A1, which is incorporated herein by
reference).
[0065] Alternatively, the sensor for monitoring the pH in the
expired breath condensate of the subject may be incorporated into a
mask or other covering of the mouth and/or nose that is worn by the
subject (see, e.g., U.S. Patent Application 2007/0068810 A1, which
is incorporated herein by reference). In some instances, the mask
may be worn at all times, and as such may continuously and in real
time measure the pH of the expired breathe condensate of a subject.
Alternatively, the mask may be worn temporarily to measure the pH
of the expired breath condensate of a subject at any given point in
time.
[0066] The method, system, or device as provided herein may further
include a sensor configured to monitor other physiological
conditions of a subject such as, pH of the pulmonary tissue or pH
of an exhalant of a subject. The sensor may be configured to
monitor further conditions which include, but are not limited to,
humidity of an exhalant, temperature, breathing rate, peak rate of
exhalation, tidal volume, vital capacity, inspiratory capacity,
expiratory reserve volume, or residual volume.
Effects of Pulmonary pH and Pharmaceutical Composition on Viral
Infection in a Subject
[0067] A method, system, or device is provided for receiving data
including data of a physical condition affecting one or more
subjects. The pH within the respiratory system, whether acidic,
neutral or basic, may contribute to susceptibility to viral
infection in terms of both target cell invasion, replication within
the target cell, and release from the target cell. A low pH
environment in endocytic and exocytic compartments of a target cell
has been shown to be a prerequisite for translocation of a viral
particle into the cell cytoplasm. Two examples of viruses that
infect the pulmonary tissue and may be influenced by pH include the
influenza viruses, associated with flu epidemics, and human
rhinoviruses, associated with the common cold. A number of other
viruses induce infection within the respiratory system and may be
influenced by the pH of the pulmonary tissue. Viruses infectious to
the respiratory system include, but are not limited to,
parainfluenza virus, coronavirus, respiratory syncytial virus,
adenovirus, cytomegalovirus, and hantavirus.
[0068] In general, three steps determine the early events in viral
infection of a host cell including adsorption to the plasma
membrane by binding to specific receptors, penetration, and
subsequent uncoating of the genome. Many enveloped and nonenveloped
viruses enter a cell via receptor-mediated endocytosis, with
membrane penetration and uncoating taking place from the endosomes.
Internalization of viral particles is initiated by invagination of
the plasma membrane. After pinching off, these vesicles derived
from the plasma membrane reach the early endosome compartment. In
early endosomes, the internalized material are either are sorted
into the recycling pathway or are directed via late endosomes to
lysosomes for degradation. Viruses are transported to the
compartment providing conditions suitable for delivery to the
cytoplasm. The low pH environment, e.g., pH 5.0 to 6.5, in
endocytic and exocytic compartments has been shown to be a
prerequisite for translocation into the cytoplasm.
[0069] Influenza virus is an enveloped negative-sense RNA virus. It
is major public health problem worldwide and is responsible for
20,000 deaths annually in the United States alone, with the
frequent emergence of new and potentially deadly strains of the
virus. As with all viruses, influenza virus needs to penetrate
target cells to cause infection. An important component of
influenza infectivity is the virally-associated surface
glycoprotein hemagglutinin which plays a role in recognition and
binding of the virus to host cells as well as fusion of the virus
with the host cell membrane. Hemagglutinin consists of a
receptor-binding (HA1) domain and a membrane-anchoring (HA2) domain
linked by a disulfide bond. Hemagglutinin selectively binds to
.alpha.-sialosides on glycoproteins and glycolipids associated with
the outer surface of the target cells. Different viral
hemagglutinins preferentially recognize different sialic
acid-galactose linkages. For example, human influenza hemagglutinin
preferentially binds alpha 2,6 linkages to galactose while the
avian H5N1 influenza hemagglutinin, for example, prefers alpha 2,3
linkages to galactose. The human lung and airway epithelial cells,
a prime target for influenza infection, have an abundance of alpha
2,6 linkages. The ability of hemagglutinin to bind to sialylated
cell surface receptors may be pH dependent.
[0070] The influenza viral particles bound to the target cells
through the interaction of hemagglutinin with sialylated cell
surface receptors are taken up by the target cell through the
process of endocytosis. The low pH environment of the endosomes
induces a large conformational change in hemagglutinin which in
turn is thought to trigger fusion between the viral and the
endosomal membranes. The optimal pH range for membrane fusion by
hemagglutinin is between 5 and 5.5. The low pH environment of the
endosome also activates the influenza virus M2 protein ion channel
which begins to conduct protons across the viral membrane. The
lowered internal virion pH is though to weaken protein-protein
interactions between the viral matrix protein (M1) and the
ribonucleoprotein (RNP) core. Preventing the release of M1 protein
results in incomplete viral uncoating and attenuated viral
replication (see, e.g., Takeda et al., J Virol. 76:1391-1399, 2002,
which is incorporated herein by reference). As such, modulating the
pH within the pulmonary tissue may influence influenza infectivity
(see, e.g., U.S. Patent Application 2008/0000473 A1, which is
incorporated herein by reference).
[0071] In some instances, lowering the pH of the pulmonary tissue
with one or more acidic agents may prevent hemagglutinin and
consequently the influenza virus from binding to the target cells
in the first place. It is conceivable that premature exposure of
virus to low pH in the extracellular environment might induce
conformational changes to glycoproteins spike on the virus surface,
thereby interfering with initial binding to the target host cell
(see, e.g., Rennie, et al., Respir. Res. 8:38, 2007, which is
incorporated herein by reference).
[0072] Human rhinoviruses, the most frequent cause of upper
respiratory tract infections known as "the common cold", may be
inactivated by acidic solutions at or below pH 5.3 (see, e.g.,
Kurht, et al., Antimicrob. Agents Chemother. 26:924-927, which is
incorporated herein by reference). Inactivation of rhinoviruses by
low pH is thought to be due to conformational changes in capsid
proteins at pH values of less than 6.2, leading to loss of the VP4
subunit of the capsid and rendering the virus noninfectious.
Treatment of mammalian cells infected with rhinovirus with acidic
solutions such as, for example, citrate/phosphate buffer (pH 5.0),
ascorbate (pH 5.0), or phthalate (pH 5.0), reduce viral titer by as
much as 90% (see, e.g., Gem, et al., J. Infect. Dis. 195:1137-1143,
2007, which is incorporated herein by reference).
[0073] Influenza viruses may also be inactivated by low pH. For
example, Influenza A Sydney/5/95 [H3N2], Influenza A Hong Kong/8/68
[H3N2] and avian reassortment virus A/Washington/897/80 X A
Mallard/New York/6750/78 [H3N2] are rapidly inactivated in vitro by
contact with acid buffered solutions at pH 3.5 (see, e.g., Rennie
et al., Respir. Res. 8:38, 2007, which is incorporated herein by
reference.
[0074] As such, modifying the pH of the pulmonary tissue with a
pharmaceutical composition configured to deliver a pH modifying
agent may prevent and/or treat a viral infection by preventing
binding, fusion, and replication of the viral particles.
Administration of the pharmaceutical composition may be informed by
sensing the pH of the pulmonary tissue of a subject.
Pharmaceutical Compositions and Particle Size
[0075] In some aspects of the methods, systems, or devices provided
herein, it may be beneficial to alter the pH, e.g., lower or raise
the pH, in one level of the pulmonary tree while maintaining the pH
in another level of the pulmonary tissue. Directing the
pharmaceutical composition to one or more levels of the pulmonary
tissue may be accomplished by varying the particle size of the one
or more agents of the pharmaceutical composition. This may be
dictated by where in the pulmonary tissue a particular viral
infection is likely to occur. For example, human rhinoviruses
commonly infect epithelial cells in the upper respiratory tract
(see, e.g., Whiteman, et al., J. Biol. Chem. 278:11954-11961, 2003,
which is incorporated herein by reference). As such, the
pharmaceutical composition may be directed specifically to the
upper respiratory tract, for example, for the prevention and
treatment of human rhinoviruses. In some instances, similar viral
strains may target host cells in different locations within the
respiratory tract (see, e.g., (see, e.g., Uiprasertkul, et al.,
Emerging Infectious Dis. 11: 1036-1041, 2005; Matrosovich, et al.,
PNAS 101:4620-4624, 2004, which are incorporated herein by
reference). For example, human influenza A specifically targets
epithelial cells in the upper respiratory tract that express the
2,6-linked sialyl-galactosyl moieties. In contrast, avian influenza
(H5N1) targets epithelial cells expressing the 2,3-linked
sialyl-galactosyl moieties. These cells in humans are primarily
located deep in the lower respiratory tract in ciliated epithelial
cells and Type II pneumocytes. The pharmaceutical composition may
be selectively directed to a level or levels of the pulmonary
tissue based on the potential viral infection site, the latter of
which is dependent upon which virus a subject has been exposed to
or may be exposed to in the future. Directing the pharmaceutical
composition to one or more levels of the pulmonary tissue may be
accomplished by varying the particle size of the one or more agents
of the pharmaceutical composition.
[0076] The pharmaceutical composition may be administered as two or
more particles sizes of the same or different pH modifying agent
for delivery to different levels of the pulmonary tissue. The two
or more particle sizes may range from approximately 1 to 4 .mu.m,
approximately 5 to 10 .mu.m, approximately 15 to 40 .mu.m, or
approximately 50 to 100 .mu.m. The two or more particle sizes may
range from approximately less than about 10 .mu.m, less than about
6 .mu.m, less than about 4 .mu.m, less than about 2 .mu.m, or less
than about 1 .mu.m. The particle size of a pharmaceutical
composition is an important variable in defining the dose deposited
and the distribution of the pharmaceutical composition in the
pulmonary tissue (see, e.g., Labiris & Dolovich, Br. J. Clin.
Pharmacol. 56:588-599, 2003, which is incorporated herein by
reference). Fine particles more readily distribute in the
peripheral airways while larger particles may deposit in the
central airways or upper respiratory tract. A particle size may be
defined by its mass median aerodynamic diameter (MMAD). Particles
may be deposited by inertial impaction, gravitational sedimentation
or diffusion depending upon their size. While deposition occurs
throughout the airways, inertial impaction generally occurs in the
first 10 generations of the lung where the air velocity is high and
flow is turbulent. Deposition by gravitational sedimentation
predominates in the last five to six generations of the airways
(smaller bronchi and bronchioles) where air velocity is low. In the
alveoli region, air velocity is negligible and as such particles
are deposited by sedimentation and diffusion. Those particles not
deposited during inhalation are exhaled.
[0077] In general, larger particles do not readily follow changes
in air flow direction and tend to deposit by inertial impaction in
the upper respiratory tract. For example, most particles greater
than 10 .mu.m are deposited in the oropharyngeal region with a
large amount impacting on the larynx. Aerosols with MMAD of 5-10
.mu.m are mainly deposited in the large conducting airways as well
as in the oropharyngeal region. Intermediate sized particles (3-5
.mu.m) are carried farther into the small airways of the bronchi
and bronchioles, with 50% of 3 .mu.m particles reaching the
alveolar region. Particles that are less than 3 .mu.m may behave
more like gas molecules following the airflow all the way to the
alveoli. However, very small particles of less the 0.5 .mu.m, for
example, may fail to be deposited in the alveoli and instead may be
exhaled.
[0078] Deposition of a pharmaceutical composition in the lungs may
also be controlled by the inspiratory flow rate, the tidal volume
and respiratory frequency of the subject (see, e.g., Labiris &
Dolovich, Br. J. Clin. Pharmacol. 56:600-612, 2003, which is
incorporated herein by reference). Controlling the air velocity or
inspiratory flow rate by slow inhalation will maximize the number
of particles that reach the alveoli and minimize the number that
are exhaled. For example, fast inhalations may result in reduced
peripheral deposition because the aerosol is more readily deposited
by inertial impaction in the conducting airway and oropharyngeal
region. When aerosols are inhaled slowly, deposition by
gravitational sedimentation in peripheral region is enhanced.
Peripheral deposition may also be increased with an increased in
tidal volume and a decrease in respiratory frequency. As such,
holding one's breath after inhalation may enable better penetration
of composition into periphery of lungs.
[0079] The particle size and deposition depth of the pharmaceutical
composition entering the lungs is a function of the inhaler device
used and the composition of the pharmaceutical composition.
Inhalers and nebulizers of different types each have the ability to
generate aerosol particles of a certain size range. For liquid
formulations containing soluble pharmaceutical compositions, the
size of the aerosol particle is largely a function of the design
and operation of the delivery device such as the nebulizer or
"atomizer" that converts the liquid into a vapor or mist. For
pharmaceutical compositions in powder form and for insoluble
pharmaceutical compositions that are suspended or dispersed in
emulsions, the particle size in the formulation of the
pharmaceutical composition is an important determining factor.
[0080] The particle size and deposition depth of the pharmaceutical
composition entering the lungs is a function of the formulation of
the pharmaceutical composition. Ideally the formulation retains the
activity of the pharmaceutical composition as well as efficiently
delivers the composition to the appropriate site of action within
the lungs and allows the composition to remain in the lungs long
enough to have the desired pharmacological effect. Formulating a
pharmaceutical composition as a dry powder for inhalation may
involve, e.g., either micronization via jet milling, precipitation,
freeze-drying or spray-drying using various excipients, such as
lipids and polymers, or carrier systems, such as lactose or other
sugars. Particles of different sizes may be generated by
modifications to the methods described above.
[0081] The size of one or more particles of the pharmaceutical
composition may be measured using any of an number of methods
including, but not limited to, light scattering, x-ray
sedimentation, electrical sensing using the Coulter principle,
sieves, spectroscopy, and microscopy combined with image analysis.
In one aspect, microscopy, e.g., optical microscopy, scanning
electron microscopy, laser scanning microscopy, confocal microscopy
or scanning probe microscopy may be combined with image analysis
software to determine the size and shape of particles (see, e.g.,
U.S. Pat. No. 7,009,169, which is incorporated herein by
reference). The Clemex Particle Size Analyzer--PS3 is an example of
a commercially available instrument for measuring particle size and
shape using microscopy and image analysis (from Clemex
Technologies, Inc., Longueuil, Canada). Another common method for
particle size determination is to use a light scattering instrument
which measures the average particle size of a population of
particles as well as the distribution of the particle size of the
particles. When light strikes a particle, scattering (diffraction)
occurs. The light scatters in all directions, but for larger
particles there is relatively more scattering to the front while
for smaller particles there is relatively more scattering to the
sides and back. The light scattering method reports a
three-dimensional (i.e., volume) equivalent sphere diameter. One
example of a commonly used light scattering instrument is the
Horiba LA-920 laser light diffraction instrument (from Horiba
Instruments, Inc., Irvine, Calif.). The light scattering method is
particularly adapted to measuring particle size and particle size
distributions of the small particles in a dispersion.
[0082] One or more particles may be sized to generate a
monodisperse population of particles. Particles that are dry powder
polydisperse powder particles, for example, may be sized using a
series of individual and or nested sieves that may further contain
beads, disks and/or other non-geometric shapes that are rotated,
vibrated or agitation in any of a number of directions to generate
monodisperse particles (see, e.g., U.S. Pat. No. 6,267,310, and
U.S. Pat. No. 6,197,835 which are incorporated herein by
reference). The monodisperse population may be characterized using
the particle size analysis methods described above.
Therapeutic Pharmaceutical Compositions
[0083] The method, system, or device as provided herein may
communicate, provide, or receive data on the environmental and/or
physiological conditions and send the data to the one or more
subjects, or to a third party, for example, a physician or other
caregiver, or to a combination thereof. Upon receiving information
regarding the environmental and/or physiological condition, a
pharmaceutical composition may be administered to the pulmonary
tissue of the subject in response to a current condition.
Alternatively, a pharmaceutical composition may be administered to
the pulmonary tissue of the subject as a prophylactic prior to
traveling to a different location for which information has been
communicated, provided, or received regarding a current or an
anticipated environmental condition. A pharmaceutical composition
may be, e.g., a basic agent, an acidic agent, or a buffering agent
to modify pulmonary pH; an antiviral agent to treat viral pulmonary
disease; or an antihistamine or decongestant to treat viral or
bacterial pulmonary disease or allergy.
[0084] Methods and compositions are provided wherein the
pharmaceutical composition may be one or more agents that may be
used to adjust the pH within the pulmonary tract of the subject.
The pharmaceutical composition may include at least one agent to a
pulmonary tissue of the subject, wherein the pharmaceutical
composition is administered as two or more distinct and
non-overlapping particle size ranges configured to contact two or
more levels of pulmonary tissue of the subject. The one or more
pharmaceutical agents may be one or more of a basic agent, an
acidic agent, a buffering agent, or some combination thereof. The
pharmaceutical composition may be one or more basic agent
comprising a proton acceptor for raising the pH in the airways such
as, for example, ammonia or bicarbonate. Alternatively, the
pharmaceutical composition may be one or more acidic agent
comprising a proton donor for lowering the pH in the airways such
as, for example, acetic acid, ascorbic acid, citric acid, phytic
acid, succinic acid, glutaric acid, phosphoric acid, or dilute
hydrochloric acid, or other proton donors. The pharmaceutical
composition may be one or more buffering agents, including, but not
limited to, sodium bicarbonate, potassium bicarbonate, phosphate
buffer, citrate buffer, lactate buffer, pyruvate buffer, phthalate
buffer, glycine (amino acetic acid), bicine
(N,N-bis(2-hydroxyethyl)glycine),
tricine(N-[tris(hydroxymethyl)methyl]glycine), CAPS
(3-(cyclohexamino)-1-propanesulphonic acid, CAPSO
(3-(cyclohexamino)-2-hydroxypropanesulphonic acid),
2-(cyclohexamino)-ethenesulphonic acid, BIS-TRIS propane, MOPS,
HEPES, DIPSO, TAPSO, TRIZMA, HEPPSO, POPSO, EPPS, dibasic sodium
phosphate, dibasic potassium phosphate, or triethanolamine.
[0085] In some instances, the pharmaceutical composition may
include one or more agents used for treating a viral infection.
Examples of agents used for treating influenza, for example,
include, but are not limited, to neuraminidase antagonists as
exemplified by zanamivir and oseltamivir and M2 viral channel
antagonists as exemplified by amantadine and rimantadine. Other
antiviral drugs of the pharmaceutical composition may include, but
are not limited to acyclovir, valacyclovir, famciclovir,
penciclovir, trifluridine, ganciclovir, valganciclovir, cidofovir,
abacavir, didanosine, emtricitabine, lamivudine, stavudine,
tenofovir, zalcitabine, zidovudine, delavirdine, efavirenz,
nevirapine, atazanavir, darunavir, fosamprenavir, indinavir,
lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir,
interferon alfa, adefovir dipivoxil, entecavir, and ribavirin.
[0086] In some instances, the pharmaceutical composition may
further include one or more agent used for treating a bacterial
infection. Examples of agents used for treating bacterial
infections include but are not limited to, beta-lactam compounds
such as penicillin, methicillin, nafcillin, oxacillin, cloxacillin,
dicloxacilin, ampicillin, ticarcillin, amoxicillin, carbenicillin,
and piperacillin; cephalosporins and cephamycins such as
cefadroxil, cefazolin, cephalexin, cephalothin, cephapirin,
cephradine, cefaclor, cefamandole, cefonicid, cefuroxime,
cefprozil, loracarbef, ceforanide, cefoxitin, cefmuetazole,
cefotetan, cefoperazone, cefotaxime, ceftazidine, ceftizoxine,
ceftriaxone, cefixime, cefpodoxime, proxetil, cefdinir, cefditoren,
pivoxil, ceftibuten, moxalactam, and cefepime; other beta-lactam
drugs such as aztreonam, clavulanic acid, sulbactam, tazobactam,
ertapenem, imipenem, and meropenem; other cell wall membrane active
agents such as vancomycin, teicoplanin, daptomycin, fosfomycin,
bacitracin, and cycloserine; tetracyclines such as tetracycline,
chlortetracycline, oxytetracycline, demeclocycline, methacycline,
doxycycline, minocycline, and tigecycline; macrolides such as
erythromycin, clarithromycin, azithromycin, and telithromycin;
aminoglycosides such as streptomycin, neomycin, kanamycin,
amikacin, gentamicin, tobramycin, sisomicin, and netilmicin;
sulfonamides such as sulfacytine, sulfisoxazole, silfamethizole,
sulfadiazine, sulfamethoxazole, sulfapyridine, and sulfadoxine;
fluoroquinolones such as ciprofloxacin, gatifloxacin, gemifloxacin,
levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, and
ofloxacin; antimycobacteria drugs such as isoniazid, rifampin,
rifabutin, rifapentine, pyrazinamide, ethambutol, ethionamide,
capreomycin, clofazimine, and dapsone; and miscellaneous
antimicrobials such as colistimethate sodium, methenamine
hippurate, methenamine mandelate, metronidazole, mupirocin,
nitrofurantoin, polymyxin B, clindamycin, choramphenicol,
quinupristin-dalfopristin, linezolid, spectrinomycin, trimethoprim,
pyrimethaimne, and trimethoprim-sulfamethoxazole.
[0087] In some instances, the pharmaceutical composition may
include one or more agents used for treating the symptoms of a
viral or bacterial infection or treating in response to an
allergen. The pharmaceutical composition may include one or more
decongestants, including, but are not limited, oxymetazoline,
phenylephrine, xylometazoline, or pseudoephedrine. The
pharmaceutical composition may also include an expectorant, e.g.,
guaifenesin. The pharmaceutical composition may further include an
antihistamine, including, but are not limited, carbinoxamine,
dimenhydrinate, diphenhydramine, tripelennamine, hydroxyzine,
cyclizine, meclizine, brompheniramine, chlorpheniramine,
promethazine, cyprohetadine, fexofenadine, loratadine, or
cetirizine.
Formulation of Pharmaceutical Compositions
[0088] Liquid Aerosol
[0089] The pharmaceutical composition may be formulated for
inhalation administration as a liquid aerosol. In this instance,
the one or more agent, e.g., one or more acidic, basic or buffering
agent, may be dissolved into an appropriate solvent. Examples of
appropriate solvents for inhalation include, but are not limited to
water, alcohols, propylene glycol.
[0090] Dry Powder
[0091] The pharmaceutical composition including at least one agent
to a pulmonary tissue of the subject, wherein the pharmaceutical
composition is administered as two or more distinct and
non-overlapping particle size ranges configured to contact two or
more levels of pulmonary tissue of the subject may be formulated
for inhalation administration as a dry powder. Formulating the
pharmaceutical composition as a dry powder for inhalation may
involve particle size reduction using jet milling, controlled
precipitation, sieving, freeze-drying or spray-drying, for example.
The pharmaceutical composition may be formulated in the absence of
added excipients. Alternatively, the pharmaceutical composition may
be formulated with added excipients. Examples of possible
excipients for dry powder formulation for inhalation include, but
are not limited to, lactose, dextran, mannitol, glucose, or a
combination thereof. The pharmaceutical composition may also
include surfactants such as oleic acid.
[0092] Liposomes
[0093] In another aspect, the pharmaceutical composition including
at least one agent to a pulmonary tissue of the subject, wherein
the pharmaceutical composition is administered as two or more
distinct and non-overlapping particle size ranges configured to
contact two or more levels of pulmonary tissue of the subject may
be formulated for inhalation as part of a liposome. Dried
phospholipids placed into an aqueous environment will spontaneously
associate into multilamellar structures that function as
permeability barriers. These lipid vesicles, termed liposomes, are
composed of aqueous compartments separated from each other and the
external medium by a series of closed concentric lipid bilayers.
The composition of the aqueous compartments is the same as the
medium in which the liposomes were formed; thus making it possible
to entrap a wide variety of materials within the lipid
bilayers.
[0094] The liposomes of the pharmaceutical composition as provided
herein may be comprised of one or more of a variety of lipids.
Suitable lipids include amphipathic lipids in which the hydrophobic
portion of the lipid material orients into a hydrophobic phase,
while the hydrophilic portion orients toward the aqueous phase.
Such compounds include, but are not limited to, phospholipids,
aminolipids, and sphingolipids. Representative phospholipids
include sphingomyelin, phosphatidylcholine,
phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol,
phosphatidic acid, palm itoyloleoyl phosphatdylcholine,
lysophosphatidylcholine, lysophosphatidylethanolamine,
dipalmitoylphosphatidylcholine, dioleoylphosphatidylcholine,
distearoylphosphatidylcholine, or dilinoleoylphosphatidylcholine.
Other phosphorus-lacking compounds, such as sphingolipids,
glycosphingolipid families, diacylglycerols, and beta-acyloxyacids,
may also be used. Additionally, such amphipathic lipids can be
readily mixed with other lipids, such as triglycerides and sterols.
Other bilayer-forming materials that may be used include long-chain
dialkyl dimethyl ammonium compounds, for example di-stearyl
dimethyl ammonium compounds such as di-stearyl dimethyl anmnonium
chloride, di-tallow dimethyl ammonium compounds such as di-tallow
dimethyl ammonium chloride and mono- and dialkyl
polyoxyethylene-derivatives. Either a single phospholipid or a
mixture of phospholipids may be used. Sterols, for example,
cholesterol or ergosterol, may be added to the liposome to increase
the stability of the liposomal bilayers and lipids possessing a
positive or negative change, for example, phosphatidylethanolamine,
gangliosides or phosphatic acid may be used to render the
appropriate charge to the liposome and to increase the size of the
aqueous compartments. Mixtures of lipids may be used to render the
liposomes more fluid or more rigid and to increase or decrease
permeability characteristics.
[0095] The liposomes of the pharmaceutical composition as provided
herein may be prepared by a variety of methods including, but not
limited to, hydration of lipid films, solvent injection,
reverse-phase evaporation, sonication, extrusion, high
pressure/homogenization, microfluidization, detergent dialysis,
calcium-induced fusion of small liposome vesicles, and
ether-infusion methods as described in, e.g., Szoka, et al., Ann.
Rev. Biophys. Bioeng., 9:467, 1980; U.S. Pat. Nos. 4,186,183,
4,217,344, 4,235,871, 4,2619975, 4,485,054, 4,501,728, 4,774,085,
4,837,028, and 4,946,787; Deamer and Bangham, Biochim. Biophys.
Acta, 443:629-634, 1976; Fraley, et al., Proc. Natl. Acad. Sci.
USA, 76:3348-3352, 1979; Hope, et al., Biochim. Biophys. Acta,
812:55-65, 1985; Mayer, et al., Biochim. Biophys. Acta,
858:161-168, 1986; Williams, et al., Proc. Natl. Acad. Sci.,
85:242-246, 1988; which are incorporated herein by reference. For
example, liposomes may be formed from a lipid film dispersing a
phospholipid or mixture of lipids in a suitable container in an
organic solvent such as, ether, chloroform, or tert-butanol, and
removing the organic solvent by methods such as evaporation, rotary
evaporation under vacuum or lyophilization with commercially
available freeze-drying equipment. Dispersing the resulting lipid
film of dry lipid powder in an aqueous medium, e.g., distilled
water, isotonic saline or buffered solutions, will result in the
formation of liposomes. In this instance, the one or more agent of
the pharmaceutical composition may be included in the aqueous
medium during the formation of the liposomes to encapsulate the one
or more agent of the pharmaceutical composition within the forming
liposomes.
[0096] The liposomes of the pharmaceutical composition as provided
herein may be administered to a subject by liquid aerosolization as
a suspension in an appropriate aqueous medium. Alternatively, the
liposomes of the pharmaceutical composition may be dried and
micronized to one or more appropriate particle size either with or
without added-exipients and administered by dry powder
inhalation.
[0097] The average size of the one or more liposomes of the
pharmaceutical composition may be less than about 10,000 nm, less
than about 8,000 nm, less than about 5000 nm, less than about 4000
nm, less than about 3000 nm, less than about 2000 mn, less than
about 1900 nm, less than about 1800 nm, less than about 1700 nm,
less than about 1600, nm, less than about 1500 nm, less than about
1400 nm, less than about 1300 nm, less than about 1200 nm, less
than about 1100 mn, less than about 1000 nm, less than about 900
nm, less than about 800 nm, less than about 700 nm, less than about
600 nm, less than about 500 nm, less than about 400 nm, less than
about 300 nm, less than about 250 nm, less than about 200 nm, less
than about 100 nm, less than about 75 nm, or less than about 50
nm.
[0098] Time or Extended Release Formulations
[0099] In some instances, the pharmaceutical composition as
provided herein may be formulated for timed release or
slow-absorbing. The pharmaceutical composition may be formulated
for timed release using one or more of a combination of liposomes.
The physiochemical properties of liposomes such as size, bilayer
fluidity, surface charge, as well as the method of preparation,
affect their in vivo behavior. The vesicle size and number of
bilayers are key parameters in determining the residence time of
liposomes. Small liposomes (.ltoreq.0.1 .mu.m), for example, are
optimized by macrophages less rapidly and to a lesser extent than
large liposomes (>0.1 .mu.m) and therefore may have a longer
half-life. Small liposomes also release their contents at a slower
rate. It should be appreciated that formulation of small liposomes
for liquid aerosol or dry powder inhalation, for example, may
include generating two or more particle sizes that are preferably
in the range of 1-10 .mu.m for optimal delivery to the pulmonary
tissue and as such each particle may itself contain multiple
smaller liposomes encapsulating the one or more agents of the
pharmaceutical composition.
[0100] Bilayer fluidity may also influence the behavior of the
liposomes. In general, lipids have a characteristic phase
transition temperature, existing in different physical states above
and below this temperature. The phase transition temperature may
range from -20.degree. C. to 90.degree. C. and is dependent upon
the length and saturation of the fatty acid side chains. Below the
phase transition temperature, the lipids are in a rigid,
well-ordered arrangement. Above the phase transition temperature,
lipids are in a liquid-crystalline state or fluid phase. As such,
liposomes composed of lipids with a phase transition temperature
above physiological temperature, e.g., above 37.degree. C., may be
less fluid and hence less likely to leak their contents. As such,
the fluidity of the liposome bilayer at various temperatures may be
used to control release of liposome contents under physiological
conditions.
[0101] Liposomes of the pharmaceutical composition may be further
modified to modulate macrophage-dependent clearance of the
liposomes from the pulmonary tissue and as such modulate residence.
In one aspect, the liposomes of the pharmaceutical composition as
provided herein may include a polymer surface coating such as
polyethylene glycol (PEG) which helps the liposome evade
recognition and uptake by the immune system and thus prolong
residence time of the pharmaceutical composition in the lung of the
subject.
[0102] In a further aspect, the pharmaceutical composition may
include formulations which release the one or more agent from the
two or more particle sizes based on the mincroenvironment of the
pulmonary tissue. In one aspect, the pharmaceutical composition may
include one or more liposome formulations in which release of the
encapsulated contents of the liposome is pH-sensitive. The
pharmaceutical composition may include polymer-caged liposomes in
which preformed liposomes are treated with a
cholesterol-functionalized poly(acrylic acid) additive,
crosslinked, to become highly stable and have tunable pH-sensitive
responses (see, e.g., Lee, et al., J. Am. Chem. Soc.
129:15096-15097, 2007, which is incorporated herein by reference).
Additional examples of pH-sensitive liposomes are further described
in Auguste, et al., J. Control Release [Epub ahead of print], 2008;
U.S. Pat. Nos. 5,786,214, 5,965,434, 6,426,086, 6,897,196,
7,229,973, which are incorporated herein by reference.
Administration of a Pharmaceutical Composition
[0103] The pharmaceutical composition including at least one agent
may be delivered by inhalation to a pulmonary tissue of the
subject, wherein the pharmaceutical composition is administered as
two or more distinct and non-overlapping particle size ranges
configured to contact two or more levels of pulmonary tissue of the
subject may be delivered by inhalation using a nebulizer. The
nebulizer may be a jet nebulizer in which compressed gas (air or
oxygen) passes through a narrow orifice creating an area of low
pressure at the outlet of an adjacent liquid feed tube. The
pharmaceutical composition in solution is drawn up from the fluid
reservoir and shattered into droplets in the gas stream.
Alternatively, the nebulizer may be an ultrasonic nebulizer in
which a piezoelectric crystal vibrates at a high frequency and
generates a fountain of liquid in the nebulizer chamber. In this
instance, the higher the frequency of vibration, the small the
droplet size.
[0104] The pharmaceutical composition as provided herein may be
delivered by inhalation using a metered liquid inhaler which
produces a fine aerosol in the respirable range by forcing the
pharmaceutical composition solution through an array of nozzles.
The pattern of holes in the nozzle as well as the size and geometry
of each hole may be modified to generate droplets of a desired
sized. These types of inhalers are exemplified by AERx (Aradigm,
Hayward, Calif., USA), AeroDose (AeroGen, Sunnyvale, Calif., USA),
and Respimat (Boehringer Ingelheim, Ingelheim, Germany).
[0105] The pharmaceutical composition may be delivered by
inhalation using a metered-dose inhaler in which the pharmaceutical
composition aerosol is driven by propellants, e.g.,
hydrofluoroalkanes. In some instances, the subject may manually
actuate the inhaler followed by appropriate inhalation.
Alternatively, the inhaler may be breath-actuated, firing in
response to the subjects inspiratory effect.
[0106] Alternatively, the pharmaceutical composition may be
delivered by inhalation using a dry powder inhaler. In this aspect,
an aerosol of the pharmaceutical composition is created by
directing air through loose powder. Dispersion of the powder into
respirable particles depends on the creation of turbulent air flow
within the powder container, causing aggregates to break up into
particles small enough to be carried into the lower airways, if
needed. The air flow may be generated by the subject.
Alternatively, a battery driven propeller or compressed air may be
used to aide in aerosolizing the powdered pharmaceutical
composition.
[0107] In some instances, the pharmaceutical composition may be
delivered directly to a subject using a personal nebulizer or
inhaler as described herein. Alternatively, the pharmaceutical
composition may be delivered to a subject or group of subjects in a
room, building or other public space. For example, West describes a
therapeutic air vent filter screen impregnated with a therapeutic
agent for use in medicating the environment in a room (WIPO Patent
WO/1999/030087, which is incorporated herein by reference). In some
instances, the pharmaceutical composition including at least one
agent to a pulmonary tissue of the subject, wherein the
pharmaceutical composition is administered as two or more distinct
and non-overlapping particle size ranges configured to contact two
or more levels of pulmonary tissue of the subject may be delivered
to a subject or group of subjects as a fine mist released into a
room or other space, e.g., an elevator, bus, train or airplane
cabin. The fine mist containing the pharmaceutical composition may
be delivered through a ventilation system. Alternatively, the fine
mist containing the pharmaceutical composition may be delivered
from one or more devices situated in the space with the flow of
mist directed towards a given subject or group of subjects. The
delivery device may be incorporated into other objects in the room
such as a computer screen or keyboard or a telephone receiver or
seat back. Alternatively, the pharmaceutical composition may be
delivered to a subject or group of subjects in a specially designed
and enclosed area. In one aspect, a fine mist may be released into
a small tent such as an oxygen tent.
[0108] The methods and compositions are further described with
reference to the following examples; however, it is to be
understood that the methods, devices, and systems are not limited
to such examples.
ILLUSTRATIVE EMBODIMENTS
Example 1
[0109] A method, system, or device is provided for receiving data
including data of a physical condition affecting a subject or a
group of subjects. The method, system, or device is further
provided for sensing the physical condition affecting the subject
or the group of subjects. Sensing the physical condition may
include, but is not limited to, sensing environmental conditions
such as smog, forest fire, volcanic ash, pollen count and weather
conditions, such as temperature and humidity. The data regarding
the physical condition may be acquired prior to the subject
entering an environment where the physical condition exists. The
method, system, or device provides data including data of the
physical condition and sends the data from a sensing device to a
receiving device on or in proximity to the subject or group of
subjects, or to a third party, e.g., a physician or other
caregiver, or to a combination thereof. Upon receiving information
regarding the physical condition, a pharmaceutical composition may
be administered in response to the physical condition wherein the
pharmaceutical composition contacts the pulmonary tissue of the
subject or group of subjects. The pharmaceutical composition
includes at least one agent and may be configured to achieve a
selected pH range in the pulmonary tissue of the one or more
subjects, for the prevention and treatment of a viral infection,
for example, prevention and treatment of influenza viral infection.
The pharmaceutical composition may include one or more buffering
agents to maintain a physiological pH in the subject or group of
subjects. Alternatively, the pharmaceutical composition may include
one or more of a basic agent, an acidic agent, or a buffering
agent, or a combination thereof, to modify pulmonary pH in the one
or more subjects. The pharmaceutical composition may be
administered as two or more distinct and non-overlapping particle
size ranges configured to contact two or more levels of pulmonary
tissue of the subject, wherein the at least one agent is configured
to achieve a selected pH range in the two or more levels of
pulmonary tissue of the subject for the prevention and treatment of
a viral infection, for example, prevention and treatment of
influenza viral infection. The pharmaceutical composition may
further include one or more antiviral agent to treat viral
pulmonary disease; one or more antihistamine or decongestant to
treat the symptoms of viral or bacterial pulmonary disease or
allergy; or a combination thereof.
[0110] A number of environment-related physical conditions may
affect lung function or susceptibility to disease including, but
not limited to, gases, particulates and other chemicals associated
with smog, forest fires and volcanic disturbance as well as
allergens, e.g., pollen and mold. Information regarding current and
projected environmental conditions may be measured in a current
location and or a future location and used to guide treatment of
the pulmonary tissue with the pharmaceutical composition.
[0111] Data regarding an environmental condition may be received by
one or more subjects from an agency or agencies that monitor and
distribute data regarding various environmental conditions. Data
regarding smog conditions in a given location may be received from
one or more sources, e.g., the Environmental Protection Agency,
NOAA-National Weather Service, NASA Earth Science, state and local
air quality monitoring agencies. Data may be automatically received
by a dedicated receiver device. Alternatively, the data may be
received by a receiving device that is part of a cell phone,
computer, personal digital assistant (PDA), pager, or other device
for receiving information. Alternatively, data regarding an
environmental condition may be sensed by a sensor associated with
or in close proximity to one or more subjects. Data regarding the
presence of unhealthy gases associated with smog, such as sulfur
dioxide, nitrogen dioxide and carbon monoxide, may be measured
using a hand held device carried by or in close proximity to one or
more subjects.
[0112] Upon receiving or sensing data indicating an environmental
condition, the device may alert one or more subjects and/or third
party caregiver of the environmental condition. The device may
provide data which recommends administration of the pharmaceutical
composition to prevent or mitigate pulmonary infection. The one or
more subjects and/or third party caregiver may choose to administer
the pharmaceutical composition. Alternatively, a delivery device
associated with the data receiving device may automatically
administer the pharmaceutical composition to one or more subjects
in response to an environmental condition. In one aspect, the
pharmaceutical composition may be administered to a single
individual using an inhaler. Alternatively, the pharmaceutical
composition may be administered to a group of subjects as a fine
mist, e.g., from a device or a ventilation system in a room or
other confined space.
[0113] The pharmaceutical composition is formulated to deliver at
least one agent to the pulmonary tissue. The pharmaceutical
composition may contain one or more buffering agent to achieve a
neutral pH of approximately 7.0 in the pulmonary tissue either in
response to current exposure or in preparation for future exposure
to a high concentration of sulfur dioxide due to poor air quality
associated with forest fire smoke or volcanic disturbance.
Example 2
[0114] A method, system, or device is provided for receiving data
including data of a physical condition affecting one or more
subjects and for providing data by sensing the physical condition
of the one or more subjects, and optionally including providing
data by sensing the physiological condition of the one or more
subjects. In one aspect, the data may inform administration of a
pharmaceutical composition to the one or more subjects in response
to the physical condition. The method, system, or device may sense
the physical condition by communicating, providing, or receiving
data on the physical condition utilizing one or more sensors
located in the airway, e.g., nostril, sinus, trachea, of the
subject. The one or more sensor may be configured to monitor pH of
the pulmonary tissue or pH of an exhalant of the subject. The one
or more sensor may be further configured to monitor one or more
parameters, including, but not limited to, humidity of an exhalant,
temperature, breathing rate, peak rate of exhalation, tidal volume,
vital capacity, inspiratory capacity, expiratory reserve volume, or
residual volume of the one or more subjects. The one or more
sensors automatically sends data to a second component of the
device, e.g., a controller. Upon receiving information regarding
the physical condition and/or the physiological condition of the
one or more subjects, the second component, e.g., the controller,
may send instructions to the device to administer a pharmaceutical
composition to the pulmonary tissue of the subject, if needed. In
one aspect, the pharmaceutical composition may include one or more
buffering agents to maintain a physiological pH in the subject or
group of subjects. Alternatively, the pharmaceutical composition
may include one or more of a basic agent, an acidic agent, or a
buffering agent, or a combination thereof, to modify pulmonary pH
in the one or more subjects. The pharmaceutical composition may
further include an antiviral agent to treat viral pulmonary
disease, or an antihistamine or decongestant to treat viral or
bacterial pulmonary disease or allergy. In a further aspect, the
pharmaceutical composition is administered as two or more distinct
and non-overlapping particle size ranges configured to contact two
or more levels of pulmonary tissue of the subject, wherein the at
least one agent is configured to achieve a selected pH range in the
two or more levels of pulmonary tissue of the subject.
[0115] The method, system, or device includes one or more sensors
that are configured to monitor a physiological condition of the
subject, e.g., the pulmonary pH. The pulmonary pH of a subject may
be measured in the exhaled breath condensate, which may consist of
aerosolized particles of the airway lining fluid, water vapor
condensation, and water soluble volatile gases. The one or more
sensors are configured to monitor the pH of the exhaled breath
condensate as an indicator of the pH of the pulmonary tissue. The
one or more sensors for monitoring pH in the exhaled breath
condensate may be sufficiently small to be located permanently or
semi-permanently in one or more location of the airway of a
subject. Alternatively, the one or more sensors may be incorporated
into a dental or nasal prosthesis or into a piece of jewelry, for
example, in a nose or tongue piercing. Alternatively, the one or
more sensor for monitoring pH may be incorporated into a mask or
other covering of the mouth and/or nose that is worn by the
subject. The mask may be worn at all times, and as such
continuously and in real time monitor exhaled breathe condensate of
a subject. Alternatively, the mask may be worn temporarily to
monitor a subject's exhaled breath condensate at any given point in
time. In another aspect, the one or more sensor for monitoring pH
may be a hand held device inserted into the oral cavity, the nasal
cavity, or a combination thereof, of the subject.
[0116] The method, system, or device may further receive data
regarding a physical condition of the subject that is an
environmental condition. The environmental condition may be a
condition posing an infectious risk. The infectious risk condition
may be directly measured using one or more sensors to monitor air
borne pathogens. Alternatively, the infectious risk condition may
be inferred from a location, a time of the year, and previous
pathogen outbreaks. In one aspect, data regarding the infection
risk condition in a given location may be communicated, provided,
or received by one or more agencies, e.g., a local or state Public
Health agency, the Centers for Disease Control (CDC), the World
Health Organization, or a combination thereof, and received by the
device and communicated to the subject and/or a third party
caregiver. The data of the infectious risk condition may be
acquired prior to the subject entering an environment where the
physical condition exists. The infectious risk condition of a
subject in combination with the pulmonary tissue pH of a subject
are communicated by the method, system, or device and may inform
administration of the pharmaceutical composition.
[0117] Upon receipt by the device of data regarding the infection
risk condition of a subject or by the device sensing data regarding
the pulmonary tissue pH of a subject, or a combination thereof, a
component of the device may analyze the incoming data and determine
that administration of the pharmaceutical composition is
appropriate under the current or predicted conditions. The device
may receive and send instructions to automatically administer the
pharmaceutical composition. Alternatively, the device may inform a
subject and/or third party caregiver of the current or predicted
conditions and the subject and/or third party caregiver may choose
to administer the pharmaceutical composition.
[0118] In one aspect, the pharmaceutical composition is
administered as two or more distinct and non-overlapping particle
size ranges configured to contact two or more levels of the
pulmonary tissue and as such achieve two or more selected pH ranges
in the two or more levels of the pulmonary tissue. In this aspect,
different pH ranges may be achieved in different levels of the
pulmonary tissue. This may facilitate directed treatment of that
level of the pulmonary tissue that is infected by a virus while
maintaining the microenvironment in other levels of the pulmonary
tissue. For example, human influenza A and human rhinoviruses
primarily infect epithelial cells in the upper airways of the
pulmonary tissue. The first particle type of the composition may
include one or more agents that is basic in pH or is a buffer that
achieves a pH of greater than 7.0 and is sized by milling,
formulation or liquid aerosolization to specifically deposit within
regions of the upper airway, trachea and bronchus, e.g., with a
diameter of about 3 to 6 .mu.m. In a further aspect, the second
particle type of the composition may achieve a pH ranging from 6.4
to 7.4 and is sized by milling, formulation, or liquid
aerosolization to a smaller diameter that enables specific deposit
within regions of the lower airway such as the bronchioles and
alveoli, e.g., with a diameter of about 1 to 2 .mu.m to maintain a
normal pH level in a pulmonary tissue of the subject.
Example 3
[0119] A method, system, or device is described for receiving data
of a physical condition affecting one or more subjects and,
optionally, for providing data by sensing the physiological
condition of the one or more subjects. The data received by the
device may include one or more of a location, a time, and a
calendar entry of one or more subjects. The device may further
receive or sense data of a physiological condition of one or more
subjects, e.g., the pH within the pulmonary tissue. The data of the
physical condition may be acquired prior to the subject entering an
environment where the physical condition exists. The method,
system, or device communicates, provides, or receives data on the
physical condition and sends the data from a sensing aspect to a
receiving aspect of the device on or in proximity to the subject or
group of subjects, or to a third party, e.g., a physician or other
caregiver, or to a combination thereof. Upon receiving information
regarding a current or future physical condition, a pharmaceutical
composition may be administered to the lungs of the subject or
group of subjects. The pharmaceutical composition includes at least
one agent and may be configured to achieve a selected pH range of
the pulmonary tissue of the one or more subjects. The
pharmaceutical composition may include one or more buffering agents
to maintain a physiological pH in the subject or group of subjects.
Alternatively, the pharmaceutical composition may include one or
more of a basic agent, an acid agent, or a buffering agent to
modify pulmonary pH in the one or more subjects. The pharmaceutical
composition may further include one or more antiviral agents to
treat viral pulmonary disease, one or more antihistamines or
decongestants to treat the symptoms of viral or bacterial pulmonary
disease or allergy, or a combination thereof.
[0120] The method, system, or device may further include a global
positioning device to monitor the current location of one or more
subjects. The method or device further includes one or more
calendar entries indicating scheduled activities, appointments,
and/or outings of one or more subjects. The location and calendar
entries may inform the device of one or more infectious risk
conditions affecting the one or more subjects. In one aspect, the
data regarding location and calendar entries may indicate when one
or more subjects enter or intend to enter a location and are liable
to be subject to increased risk of contracting a viral infection. A
location with an increased risk of contracting a viral infection
may be a crowded public space including, but not limited to, an
airplane, a bus, a train, an office, a crowded city, a medical
facility, a school, or a childcare facility. The method, system, or
device may further receive data regarding current or anticipated
pathogen outbreaks in a given location and at a given time of the
year. As such, the location with an increased risk of contracting a
viral infection may be a specific country and/or a specific
location within that country.
[0121] The method, system, or device may further include one or
more sensors for monitoring a physiological condition of one or
more subjects. The method, system, or device may include sensors
for monitoring the pulmonary pH of one or more subjects as provided
herein. The infectious risk condition of one or more subjects is
informed by data regarding the location and/or calendar entries of
the one or more subjects in combination with data regarding the
pulmonary tissue pH of the one or more subjects. These data are
communicated by the method, system, or device and may inform
administration of the pharmaceutical composition to the one or more
subjects.
[0122] Upon receipt of data regarding the location and/or calendar
entries of one or more subjects, or upon receipt of sensing data
regarding the pulmonary tissue pH of a subject or group of
subjects, or a combination thereof, a component of the device may
analyze the incoming data and determine that administration of the
pharmaceutical composition to the one or more subjects is
appropriate under the current or predicted conditions. The device
may provide instructions to automatically administer the
pharmaceutical composition. Alternatively, the device may inform
one or more subjects and/or third party caregiver of the current or
predicted conditions and the one or more subjects and/or third
party caregiver may choose to administer the pharmaceutical
composition. In one aspect, a calendar entry and/or a location may
indicate that a subject is about to board an airplane during a time
of the year indicated as "flu season" by data received from a
monitoring agency. In addition, one or more sensors may indicate
that the subject's current pulmonary pH is below the normal pH
range. Upon receiving this data, a component of the device worn by
the subject, e.g., a dental prosthesis, may receive instructions to
administer the pharmaceutical composition to the one or more
subjects. Alternatively, the subject may receive this data from the
device and actively choose to administer the pharmaceutical
composition using, e.g., a hand-held inhaler.
[0123] Each recited range includes all combinations and
sub-combinations of ranges, as well as specific numerals contained
therein.
[0124] All publications and patent applications cited in this
specification are herein incorporated by reference to the extent
not inconsistent with the description herein and for all purposes
as if each individual publication or patent application were
specifically and individually indicated to be incorporated by
reference for all purposes.
[0125] The herein described components (e.g., steps), devices, and
objects and the description accompanying them are used as examples
for the sake of conceptual clarity and that various configuration
modifications using the disclosure provided herein are within the
skill of those in the art. Consequently, as used herein, the
specific exemplars set forth and the accompanying description are
intended to be representative of their more general classes. In
general, use of any specific exemplar herein is also intended to be
representative of its class, and the non-inclusion of such specific
components (e.g., steps), devices, and objects herein should not be
taken as indicating that limitation is desired.
[0126] With respect to the use of substantially any plural or
singular terms herein, those having skill in the art can translate
from the plural to the singular or from the singular to the plural
as is appropriate to the context or application. The various
singular/plural permutations are not expressly set forth herein for
sake of clarity.
[0127] The herein described subject matter sometimes illustrates
different components contained within, or connected with, different
other components. It is to be understood that such depicted
architectures are merely exemplary, and that in fact many other
architectures can be implemented which achieve the same
functionality. In a conceptual sense, any arrangement of components
to achieve the same functionality is effectively "associated" such
that the desired functionality is achieved. Hence, any two
components herein combined to achieve a particular functionality
can be seen as "associated with" each other such that the desired
functionality is achieved, irrespective of architectures or
intermedial components. Likewise, any two components so associated
can also be viewed as being "operably connected," or "operably
coupled," to each other to achieve the desired functionality, and
any two components capable of being so associated can also be
viewed as being "operably couplable", to each other to achieve the
desired functionality. Specific examples of operably couplable
include but are not limited to physically mateable or physically
interacting components or wirelessly interactable or wirelessly
interacting components or logically interacting or logically
interactable components.
[0128] While particular aspects of the present subject matter
described herein have been shown and described, it will be apparent
to those skilled in the art that, based upon the teachings herein,
changes and modifications may be made without departing from the
subject matter described herein and its broader aspects and,
therefore, the appended claims are to encompass within their scope
all such changes and modifications as are within the true spirit
and scope of the subject matter described herein. Furthermore, it
is to be understood that the invention is defined by the appended
claims. It will be understood that, in general, terms used herein,
and especially in the appended claims (e.g., bodies of the appended
claims) are generally intended as "open" terms (e.g., the term
"including" should be interpreted as "including but not limited
to," the term "having" should be interpreted as "having at least,"
the term "includes" should be interpreted as "includes but is not
limited to," etc.). It will be further understood that if a
specific number of an introduced claim recitation is intended, such
an intent will be explicitly recited in the claim, and in the
absence of such recitation no such intent is present. For example,
as an aid to understanding, the following appended claims may
contain usage of the introductory phrases "at least one" and "one
or more" to introduce claim recitations. However, the use of such
phrases should not be construed to imply that the introduction of a
claim recitation by the indefinite articles "a" or "an" limits any
particular claim containing such introduced claim recitation to
inventions containing only one such recitation, even when the same
claim includes the introductory phrases "one or more" or "at least
one" and indefinite articles such as "a" or "an"; the same holds
true for the use of definite articles used to introduce claim
recitations. In addition, even if a specific number of an
introduced claim recitation is explicitly recited, such recitation
should typically be interpreted to mean at least the recited number
(e.g., the bare recitation of "two recitations," without other
modifiers, typically means at least two recitations, or two or more
recitations). Furthermore, in those instances where a convention
analogous to "at least one of A, B, and C, etc." is used, in
general such a construction is intended in the sense one having
skill in the art would understand the convention (e.g., "a system
having at least one of A, B, and C" would include but not be
limited to systems that have A alone, B alone, C alone, A and B
together, A and C together, B and C together, or A, B, and C
together, etc.). In those instances where a convention analogous to
"at least one of A, B, or C, etc." is used, in general such a
construction is intended in the sense one having skill in the art
would understand the convention (e.g., "a system having at least
one of A, B, or C" would include but not be limited to systems that
have A alone, B alone, C alone, A and B together, A and C together,
B and C together, or A, B, and C together, etc.). Virtually any
disjunctive word and/or phrase presenting two or more alternative
terms, whether in the description, claims, or drawings, should be
understood to contemplate the possibilities of including one of the
terms, either of the terms, or both terms. For example, the phrase
"A or B" will be understood to include the possibilities of "A" or
"B" or "A and B."
[0129] While various aspects and embodiments have been disclosed
herein, other aspects and embodiments will be apparent to those
skilled in the art. The various aspects and embodiments disclosed
herein are for purposes of illustration and are not intended to be
limiting, with the true scope and spirit being indicated by the
following claims.
* * * * *
References