U.S. patent application number 12/388455 was filed with the patent office on 2009-08-20 for devices and methods for delivery of a therapeutic agent through a pneumostoma.
This patent application is currently assigned to Portaero, Inc.. Invention is credited to David C. Plough, Don Tanaka, Joshua P. Wiesman.
Application Number | 20090205658 12/388455 |
Document ID | / |
Family ID | 40953964 |
Filed Date | 2009-08-20 |
United States Patent
Application |
20090205658 |
Kind Code |
A1 |
Tanaka; Don ; et
al. |
August 20, 2009 |
DEVICES AND METHODS FOR DELIVERY OF A THERAPEUTIC AGENT THROUGH A
PNEUMOSTOMA
Abstract
A pneumostoma management system includes a pneumostoma
management device for maintaining the patency of a pneumostoma and
a drug delivery device for pneumostoma care. The drug delivery
device includes a therapeutic agent dispenser for supplying a
therapeutic agent and a propellant at positive pressure, a tube for
entering the pneumostoma and a limiting device for limiting the
depth of insertion of the tube into a pneumostoma. The drug
delivery device may be used to introduce therapeutic agents into
the pneumostoma for direct treatment of the pneumostoma, treatment
of the lung by way of collateral ventilation, and/or treatment of
non-lung tissues by diffusion into the bloodstream.
Inventors: |
Tanaka; Don; (Saratoga,
CA) ; Plough; David C.; (Portola Valley, CA) ;
Wiesman; Joshua P.; (Boston, MA) |
Correspondence
Address: |
FLIESLER MEYER LLP
650 CALIFORNIA STREET, 14TH FLOOR
SAN FRANCISCO
CA
94108
US
|
Assignee: |
Portaero, Inc.
cupertino
CA
|
Family ID: |
40953964 |
Appl. No.: |
12/388455 |
Filed: |
February 18, 2009 |
Related U.S. Patent Documents
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Application
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61029830 |
Feb 19, 2008 |
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61032877 |
Feb 29, 2008 |
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61038371 |
Mar 20, 2008 |
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61082892 |
Jul 23, 2008 |
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61083573 |
Jul 25, 2008 |
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61084559 |
Jul 29, 2008 |
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61088118 |
Aug 12, 2008 |
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61143298 |
Jan 8, 2009 |
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61151581 |
Feb 11, 2009 |
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Current U.S.
Class: |
128/203.15 ;
604/257; 604/500 |
Current CPC
Class: |
A61M 25/04 20130101;
A61M 2205/7536 20130101; A61M 13/00 20130101; A61M 16/0816
20130101; A61M 16/0833 20140204; A61M 15/009 20130101; A61K 9/007
20130101; A61M 11/005 20130101; A61M 2202/0208 20130101; A61M 25/10
20130101; A61M 11/042 20140204; A61M 2205/7518 20130101; A61M 15/02
20130101; A61M 39/0247 20130101; A61M 2039/0252 20130101; A61M
25/02 20130101; A61M 39/02 20130101; A61B 2017/00809 20130101; A61M
15/0085 20130101; A61M 2202/064 20130101; A61M 27/00 20130101; A61M
2202/025 20130101; A61M 2205/075 20130101; A61M 16/202 20140204;
A61M 2039/0276 20130101; A61M 11/00 20130101; A61M 1/04
20130101 |
Class at
Publication: |
128/203.15 ;
604/257; 604/500 |
International
Class: |
A61M 15/00 20060101
A61M015/00; A61M 31/00 20060101 A61M031/00 |
Claims
1. A therapeutic agent delivery device adapted to treat a patient
comprising: a tube having a proximal end and a distal end adapted
to be inserted into a pneumostoma; a flange connected to the tube
to limit insertion of the tube into the pneumostoma; a container
selectably connectable to the proximal end of the tube and adapted
to include one or more doses of the therapeutic agent; and an
actuator which is adapted to release at least a portion of the
therapeutic agent and provide the at least a portion of the
therapeutic agent suspended in a gas into the proximal end of the
tube; an aperture in the distal end of the tube adapted to release
the at least a portion of the therapeutic agent suspended in a gas
into the pneumostoma.
2. The therapeutic agent delivery device of claim 1, further
comprising: a source of positive pressure gas wherein the positive
pressure gas is adapted to transport the at least a portion of the
therapeutic agent suspended in a gas through the aperture in the
distal end of the tube into the pneumostoma.
3. The therapeutic agent delivery device of claim 1, further
comprising: a pressurized gas canister wherein the pressurized gas
is adapted to transport the at least a portion of the therapeutic
agent suspended in a gas through the aperture in the distal end of
the tube into the pneumostoma.
4. The therapeutic agent delivery device of claim 1, adapted to
permit the at least a portion of the therapeutic agent suspended in
a gas to be sucked through the aperture in the distal end of the
tube into the pneumostoma by negative pressure created in the
pneumostoma when the patient inhales.
5. The therapeutic agent delivery device of claim 1, wherein, upon
actuation, the actuator release a metered dose of the therapeutic
agent.
6. The therapeutic agent delivery device of claim 1, wherein: the
flange is adapted to be releasably secured to skin of the patient
surrounding the pneumostoma; the flange comprises an aperture
through which the distal end of the tube may be inserted into the
pneumostoma; the flange comprises a coupling to connect the tube to
the flange to limit insertion of the tube into the pneumostoma.
7. The therapeutic agent delivery device of claim 1, wherein the
flange and the tube are formed in one piece.
8. The therapeutic agent delivery device of claim 1, wherein: the
flange and the tube are formed in one piece; the flange is adapted
to be releasably secured to the skin of the patient surrounding the
pneumostoma; and wherein the therapeutic agent delivery device
further comprises a releasable coupling which releasably connects
the container and actuator to the tube.
9. The therapeutic agent delivery device of claim 1, further
comprising a nebulizer mechanism to produce an aerosol of the
therapeutic agent.
10. The therapeutic agent delivery device of claim 1, in
combination with a plurality of doses of a therapeutic agent.
11. A drug delivery device for treating a patient comprising: a
tube having a proximal end and a distal end adapted to be inserted
into a pneumostoma; a flange connected to the tube to limit
insertion of the tube into the pneumostoma; a therapeutic agent
dispenser adapted to provide a dose of a therapeutic agent
suspended in a gas into the proximal end of the tube; an aperture
in the distal end of the tube adapted to release the dose of a
therapeutic agent suspended in a gas into the pneumostoma.
12. The drug delivery device of claim 11, further comprising: a
source of positive pressure gas wherein the positive pressure gas
is adapted to transport the dose of a therapeutic agent suspended
in a gas through the aperture in the distal end of the tube into
the pneumostoma.
13. The drug delivery device of claim 11, further comprising: a
pressurized gas canister wherein the pressurized gas is adapted to
transport the dose of a therapeutic agent suspended in a gas
through the aperture in the distal end of the tube into the
pneumostoma.
14. The drug delivery device of claim 11, adapted to permit the
dose of a therapeutic agent suspended in a gas to be sucked through
the aperture in the distal end of the tube into the pneumostoma by
the negative pressure created in the pneumostoma when the patient
inhales.
15. The drug delivery device of claim 11, further comprising an
actuator wherein, upon actuation, the actuator causes the
therapeutic agent dispenser to provide a dose of a therapeutic
agent suspended in a gas into the proximal end of the tube.
16. The drug delivery device of claim 11, wherein: the flange is
adapted to be releasably secured to skin of the patient surrounding
the pneumostoma; the flange comprises an aperture through which the
distal end of the tube may be inserted into the pneumostoma; the
flange comprises a coupling to connect the tube to the flange to
limit insertion of the tube into the pneumostoma.
17. The drug delivery device of claim 11, wherein: the flange and
the tube are formed in one piece; the flange is adapted to be
releasably secured to the skin of the patient surrounding the
pneumostoma; and wherein the drug delivery device further comprises
a releasable coupling which releasably connects the container and
actuator to the tube.
18. The drug delivery device of claim 11, wherein the therapeutic
agent dispenser comprises a nebulizer.
19. The drug delivery device of claim 11, in combination with a
plurality of doses of a therapeutic agent.
20. A method to deliver a therapeutic agent into a pneumostoma
wherein the method comprises: providing a drug delivery device
comprising a tube having a proximal end and a distal end adapted to
be inserted into the pneumostoma, a flange connected to the tube, a
therapeutic agent dispenser connected to the tube and adapted to
provide a dose of a therapeutic agent suspended in a gas into the
tube, and an aperture in the distal end of the tube adapted to
release the dose of a therapeutic agent suspended in a gas into a
pneumostoma; and providing instructions for use of the drug
delivery device wherein the instructions for use include steps of:
(a) inserting the distal end of the tube into the pneumostoma until
the flange engages a chest of the patient; (b) actuating
therapeutic agent dispenser to provide a dose of therapeutic agent
into the pneumostoma; and (c) removing the distal end of the tube
from the pneumostoma.
Description
CLAIM TO PRIORITY
[0001] This application claims priority to all of the following
applications including: U.S. Provisional Application No.
61/029,830, filed Feb. 19, 2008, entitled "ENHANCED PNEUMOSTOMA
MANAGEMENT DEVICE AND METHODS FOR TREATMENT OF CHRONIC OBSTRUCTIVE
PULMONARY DISEASE" (Attorney Docket No. LUNG1-06013US0);
[0002] U.S. Provisional Application No. 61/032,877, filed Feb. 29,
2008, entitled "PNEUMOSTOMA MANAGEMENT SYSTEM AND METHODS FOR
TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE" (Attorney
Docket No. LUNG1-06001US0);
[0003] U.S. Provisional Application No. 61/038,371, filed Mar. 20,
2008, entitled "SURGICAL PROCEDURE AND INSTRUMENT TO CREATE A
PNEUMOSTOMA AND TREAT CHRONIC OBSTRUCTIVE PULMONARY DISEASE"
(Attorney Docket No. LUNG1-06000US0);
[0004] U.S. Provisional Application No. 61/082,892, filed Jul. 23,
2008, entitled "PNEUMOSTOMA MANAGEMENT SYSTEM HAVING A COSMETIC
AND/OR PROTECTIVE COVER" (Attorney Docket No. LUNG1-06008US0);
[0005] U.S. Provisional Application No. 61/083,573, filed Jul. 25,
2008, entitled "DEVICES AND METHODS FOR DELIVERY OF A THERAPEUTIC
AGENT THROUGH A PNEUMOSTOMA" (Attorney Docket No.
LUNG1-06003US0);
[0006] U.S. Provisional Application No. 61/084,559, filed Jul. 29,
2008, entitled "ASPIRATOR FOR PNEUMOSTOMA MANAGEMENT" (Attorney
Docket No. LUNG1-06011US0);
[0007] U.S. Provisional Application No. 61/088,118, filed Aug. 12,
2008, entitled "FLEXIBLE PNEUMOSTOMA MANAGEMENT SYSTEM AND METHODS
FOR TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE" (Attorney
Docket No. LUNG1-06004US0);
[0008] U.S. Provisional Application No. 61/143,298, filed Jan. 8,
2009, entitled "METHODS AND APPARATUS FOR THE CRYOTHERAPY CREATION
OR RE-CREATION OF PNEUMOSTOMY" (Attorney Docket No.
LUNG1-06006US0); and
[0009] U.S. Provisional Application No. 61/151,581, filed Feb. 11,
2009, entitled "SURGICAL INSTRUMENTS AND PROCEDURES TO CREATE A
PNEUMOSTOMA AND TREAT CHRONIC OBSTRUCTIVE PULMONARY DISEASE"
(Attorney Docket No. LUNG1-06002US0).
[0010] All of the afore-mentioned applications are incorporated
herein by reference in their entireties.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0011] This application is related to all of the above provisional
applications and all the patent applications that claim priority
thereto including:
[0012] This application is related to all of the following
applications including U.S. patent application Ser. No. 12/______,
filed Feb. 18, 2009, entitled "ENHANCED PNEUMOSTOMA MANAGEMENT
DEVICE AND METHODS FOR TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY
DISEASE" (Attorney Docket No. LUNG1-06013US1);
[0013] U.S. patent application Ser. No. 12/______, filed Feb. 18,
2009, entitled "PNEUMOSTOMA MANAGEMENT SYSTEM AND METHODS FOR
TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE" (Attorney
Docket No. LUNG1-06001US1);
[0014] U.S. patent application Ser. No. 12/______, filed Feb. 18,
2009, entitled "PNEUMOSTOMA MANAGEMENT METHOD FOR TREATMENT OF
CHRONIC OBSTRUCTIVE PULMONARY DISEASE" (Attorney Docket No.
LUNG1-06001US2);
[0015] U.S. patent application No. Ser. 12/______, filed Feb. 18,
2009, entitled "TWO-PHASE SURGICAL PROCEDURE FOR CREATING A
PNEUMOSTOMA TO TREAT CHRONIC OBSTRUCTIVE PULMONARY DISEASE"
(Attorney Docket No. LUNG1-06000US1);
[0016] U.S. patent application Ser. No. 12/______, filed Feb. 18,
2009, entitled "ACCELERATED TWO-PHASE SURGICAL PROCEDURE FOR
CREATING A PNEUMOSTOMA TO TREAT CHRONIC OBSTRUCTIVE PULMONARY
DISEASE" (Attorney Docket No. LUNG1-06000US2);
[0017] U.S. patent application Ser. No. 12/______, filed Feb. 18,
2009, entitled "SINGLE-PHASE SURGICAL PROCEDURE FOR CREATING A
PNEUMOSTOMA TO TREAT CHRONIC OBSTRUCTIVE PULMONARY DISEASE"
(Attorney Docket No. LUNG1-06000US3);
[0018] U.S. patent application Ser. No. 12/______, filed Feb. 18,
2009, entitled "PERCUTANEOUS SINGLE-PHASE SURGICAL PROCEDURE FOR
CREATING A PNEUMSOTOMA TO TREAT CHRONIC OBSTRUCTIVE PULMONARY
DISEASE" (Attorney Docket No. LUNG1-06000US4);
[0019] U.S. patent application Ser. No. 12/______, filed Feb. 13,
2009, entitled "PNEUMOSTOMA MANAGEMENT SYSTEM HAVING A COSTMETIC
AND/OR PROTECTIVE COVER" (Attorney Docket No. LUNG1-06008US1)
[0020] U.S. patent application Ser. No. 12/______, filed Feb. 18,
2009, entitled "ASPIRATOR FOR PNEUMOSTOMA MANAGEMENT" (Attorney
Docket No. LUNG1-06011US1);
[0021] U.S. patent application Ser. No. 12/______, filed Feb. 18,
2009, entitled "ASPIRATOR AND METHOD FOR PNEUMOSTOMA MANAGEMENT"
(Attorney Docket No. LUNG1-06011US2);
[0022] U.S. patent application Ser. No. 12/______, filed Feb. 18,
2009, entitled "FLEXIBLE PNEUMOSTOMA MANAGEMENT SYSTEM AND METHODS
FOR TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE" (Attorney
Docket No. LUNG1-06004US1);
[0023] U.S. patent application Ser. No. 12/______, filed Feb. 18,
2009, entitled "METHODS AND DEVICES FOR FOLLOW-UP CARE AND
TREATMENT OF A PNEUMOSTOMA" (Attorney Docket No.
LUNG1-06006US1);
[0024] U.S. patent application Ser. No. 12/______, filed Feb. 18,
2009, entitled "SURGICAL INSTRUMENTS FOR CREATING A PNEUMOSTOMA AND
TREATING CHRONIC OBSTRUCTIVE PULMONARY DISEASE" (Attorney Docket
No. LUNG1-06002US1);
[0025] U.S. patent application Ser. No. 12/______, filed Feb. 18,
2009, entitled "ONE-PIECE PNEUMOSTOMA MANAGEMENT SYSTEM AND METHODS
FOR TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE" (Attorney
Docket No. LUNG1-06017US1);
[0026] U.S. patent application Ser. No. 12/______, filed Feb. 18,
2009, entitled "PNEUMOSTOMA MANAGEMENT SYSTEM WITH SECRETION
MANAGEMENT FEATURES FOR TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY
DISEASE" (Attorney Docket No. LUNG1-06019US1);
[0027] U.S. patent application Ser. No. 12/______, filed Feb. 18,
2009, entitled "MULTI-LAYER PNEUMOSTOMA MANAGEMENT SYSTEM AND
METHODS FOR TREATMENT OF CHRONIC OBSTRUCTIVE PULJMONARY DISEASE"
(Attorney Docket No. LUNG1-06022US1);
[0028] U.S. patent application Ser. No. 12/______, filed Feb. 18,
2009, entitled "VARIABLE LENGTH PNEUMOSTOMA MANAGEMENT SYSTEM FOR
TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE" (Attorney
Docket No. LUNG1-06023US1); and
[0029] U.S. patent application Ser. No. 12/______, filed Feb. 18,
2009, entitled "SELF-SEALING DEVICE AND METHOD FOR DELIVERY OF A
THERAPEUTIC AGENT THROUGH A PNEUMOSTOMA" (Attorney Docket No.
LUNG1-06025US1).
[0030] All of the afore-mentioned applications are incorporated
herein by reference in their entireties. This patent application
also incorporates by reference in their entireties all patents,
applications, and articles discussed and/or cited herein.
BACKGROUND OF THE INVENTION
[0031] In the United States alone, approximately 14 million people
suffer from some form of Chronic Obstructive Pulmonary Disease
(COPD). However an additional ten million adults have evidence of
impaired lung function indicating that COPD may be significantly
underdiagnosed. The cost of COPD to the nation in 2002 was
estimated to be $32.1 billion. Medicare expenses for COPD
beneficiaries were nearly 2.5 times that of the expenditures for
all other patients. Direct medical services accounted for $18.0
billion, and indirect cost of morbidity and premature mortality was
$14.1 billion. COPD is the fourth leading cause of death in the
U.S. and is projected to be the third leading cause of death for
both males and females by the year 2020.
[0032] Chronic Obstructive Pulmonary Disease (COPD) is a
progressive disease of the airways that is characterized by a
gradual loss of lung function. In the United States, the term COPD
includes chronic bronchitis, chronic obstructive bronchitis, and
emphysema, or combinations of these conditions. In emphysema the
alveoli walls of the lung tissue are progressively weakened and
lose their elastic recoil. The breakdown of lung tissue causes
progressive loss of elastic recoil and the loss of radial support
of the airways which traps residual air in the lung. This increases
the work of exhaling and leads to hyperinflation of the lung. When
the lungs become hyperinflated, forced expiration cannot reduce the
residual volume of the lungs because the force exerted to empty the
lungs collapses the small airways and blocks air from being
exhaled. As the disease progresses, the inspiratory capacity and
air exchange surface area of the lungs is reduced until air
exchange becomes seriously impaired and the individual can only
take short shallow labored breaths (dyspnea).
[0033] The symptoms of COPD can range from the chronic cough and
sputum production of chronic bronchitis to the severe disabling
shortness of breath of emphysema. In some individuals, chronic
cough and sputum production are the first signs that they are at
risk for developing the airflow obstruction and shortness of breath
characteristic of COPD. With continued exposure to cigarettes or
noxious particles, the disease progresses and individuals with COPD
increasingly lose their ability to breathe. Acute infections or
certain weather conditions may temporarily worsen symptoms
(exacerbations), occasionally where hospitalization may be
required. In others, shortness of breath may be the first
indication of the disease. The diagnosis of COPD is confirmed by
the presence of airway obstruction on testing with spirometry.
Ultimately, severe emphysema may lead to severe dyspnea, severe
limitation of daily activities, illness and death.
[0034] There is no cure for COPD or pulmonary emphysema, only
various treatments for ameliorating the symptoms. The goal of
current treatments is to help people live with the disease more
comfortably and to prevent the progression of the disease. The
current options include: self-care (e.g., quitting smoking),
therapeutic agents (such as bronchodilators which do not address
emphysema physiology), long-term oxygen therapy, and surgery (lung
transplantation and lung volume reduction surgery). Lung Volume
Reduction Surgery (LVRS) is an invasive procedure primarily for
patients who have a localized (heterogeneous) version of emphysema;
in which, the most diseased area of the lung is surgically removed
to allow the remaining tissue to work more efficiently. Patients
with diffuse emphysema cannot be treated with LVRS, and typically
only have lung transplantation as an end-stage option. However,
many patients are not candidates for such a taxing procedure.
[0035] A number of less-invasive surgical methods have been
proposed for ameliorating the symptoms of COPD. In one approach new
windows are opened inside the lung to allow air to more easily
escape from the diseased tissue into the natural airways. These
windows are kept open with permanently implanted stents. Other
approaches attempt to seal off and shrink portions of the
hyperinflated lung using chemical treatments and/or implantable
plugs. However, these proposals remain significantly invasive and
are still in clinical trails. None of the surgical approaches to
treatment of COPD has been widely adopted. Therefore, a large unmet
need remains for a medical procedure that can sufficiently
alleviate the debilitating effects of COPD and emphysema and is
accepted by physicians and patients.
[0036] Additionally, respiratory diseases like asthma and COPD are
typically treated with inhaled therapeutic agents in order to
relieve bronchoconstriction and inflammation in the lung tissue.
There are several advantages to administering these therapeutic
agents via the inhaled route compared to oral therapy including for
example, a faster onset of action, lower therapeutic agent doses
and a better efficacy to-safety ratio therapeutic agent delivery by
inhalation is also painless and is more convenient than injectable
therapeutic agents and thus patient acceptance and compliance is
more likely. However, delivery of therapeutic agents into lung
tissue is difficult in asthma and COPD treatment because some
patients cannot take the deep breathe necessary to inhale an
therapeutic agent aerosol or therapeutic agent powder deep into the
lung. Also many of the inhaler device are difficult to operate.
Significant and variable amounts of the therapeutic agent are
filtered and/or absorbed in the upper respiratory tract. Thus
inhaled therapeutic agent delivery is difficult of impossible in
the very patients that would benefit most.
SUMMARY OF THE INVENTION
[0037] In view of the disadvantages of the state of the art,
Applicants have developed a method for treating COPD in which an
artificial passageway is made through the chest wall into the lung.
An anastomosis is formed between the artificial passageway and the
lung by creating a pleurodesis between the visceral and parietal
membranes surrounding the passageway as it enters the lung. The
pleurodesis prevents air from entering the pleural cavity and
causing a pneumothorax (deflation of the lung due to air pressure
in the pleural cavity). The pleurodesis is stabilized by a fibrotic
healing response between the membranes. The artificial passageway
through the chest wall also becomes epithelialized. The result is a
stable artificial aperture through the chest wall which
communicates with the parenchymal tissue of the lung.
[0038] The artificial aperture into the lung through the chest is
referred to herein as a pneumostoma. A pneumostoma provides an
extra pathway that allows air to exit the lung while bypassing the
natural airways which have been impaired by COPD and emphysema. By
providing this ventilation bypass, the pneumostoma allows the stale
air trapped in the lung to escape from the lung thereby shrinking
the lung (reducing hyperinflation). By shrinking the lung, the
ventilation bypass reduces breathing effort (reducing dyspnea),
allows more fresh air to be drawn in through the natural airways
and increases the effectiveness of all of the tissues of the lung
for gas exchange. Increasing the effectiveness of gas exchange
allows for increased absorption of oxygen into the bloodstream and
also increased removal of carbon dioxide. Reducing the amount of
carbon dioxide retained in the lung reduces hypercapnia which also
reduces dyspnea. The pneumostoma thereby achieves the advantages of
lung volume reduction surgery without surgically removing or
sealing off a portion of the lung.
[0039] In accordance with an embodiment, the present invention
provides a pneumostoma management system including a pneumostoma
management device and a drug delivery device which interacts with
one or more components of the pneumostoma management device to
safely and effectively apply therapeutic agent delivery to a
pneumostoma. The drug delivery device delivers a therapeutic agent
aerosol or therapeutic agent powder deep into the parenchymal
tissue of the lung. Therapeutic agents are not lost to filtration
in the respiratory tract and thus the delivery is less variable. As
a consequence, dosage is more controlled and can be reduced
compared to dosage required by other delivery methods such as oral
or inhaled.
[0040] In accordance with a general embodiment, the present
invention provides a drug delivery device and method to safely and
effectively apply therapeutic agent delivery to a pneumostoma.
[0041] In accordance with one embodiment, the present invention
provides a pneumostoma management system which includes a
partially-implantable pneumostoma vent, a chest mount and a drug
delivery device. The drug delivery device attaches to the chest
mount to safely and effectively apply therapeutic agent delivery to
a pneumostoma.
[0042] In accordance with one embodiment, the present invention
provides a pneumostoma management system which includes a
partially-implantable pneumostoma vent, a chest mount and drug
delivery device. The chest mount is secured to the skin of the
patient. The drug delivery device attaches to the chest mount in
the absence of the pneumostoma vent.
[0043] In accordance with one embodiment, the present invention
provides a pneumostoma management system which includes a
partially-implantable pneumostoma vent, a chest mount and drug
delivery device. The chest mount is secured to the skin of the
patient. The partially-implantable pneumostoma vent is placed into
a pneumostoma through an aperture in the chest mount. The drug
delivery device attaches to the pneumostoma vent while it is
mounted in the chest mount.
[0044] In accordance with embodiments of the present invention the
drug delivery device provides a therapeutic agent in a vapor,
aerosolized solution, suspended powder. The therapeutic agent is
then introduced into the pneumostoma using a pressure differential
between the drug delivery device and the pneumostoma. In some cases
a positive pressure may be applied by the drug delivery device. In
other cases the drug delivery device remains at or near ambient
pressure and the pressure differential is the result of reduced
pressure in the pneumostoma during inhalation by the patient.
[0045] In accordance with a specific embodiment of the present
invention provides a therapeutic agent delivery device which
includes: a tube having a proximal end and a distal end adapted to
be inserted into a pneumostoma; an aperture in the distal end of
the tube adapted to release the at least a portion of the
therapeutic agent suspended in a gas into the pneumostoma; a flange
connected to the tube to limit insertion of the tube into the
pneumostoma; a container selectably connectable to the proximal end
of the tube and adapted to include one or more doses of the
therapeutic agent; and an actuator which is adapted to release at
least a portion of the therapeutic agent and provide the at least a
portion of the therapeutic agent suspended in a gas into the
proximal end of the tube. Actuation of the actuator provides the
therapeutic agent into via the tube into the pneumostoma.
[0046] Thus, various systems, components and methods are provided
for managing a pneumostoma and thereby treating COPD. Other
objects, features and advantages of the invention will be apparent
from drawings and detailed description to follow.
BRIEF DESCRIPTION OF THE DRAWINGS
[0047] The above and further features, advantages and benefits of
the present invention will be apparent upon consideration of the
present description taken in conjunction with the accompanying
drawings.
[0048] FIG. 1A shows the chest of a patient indicating alternative
locations for a pneumostoma that may be managed using the device
and methods of the present invention.
[0049] FIG. 1B shows a sectional view of the chest illustrating the
relationship between the pneumostoma, lung and natural airways.
[0050] FIG. 1C shows a detailed sectional view of a
pneumostoma.
[0051] FIG. 2A shows a perspective view of components of a
pneumostoma management device according to an embodiment of the
present invention.
[0052] FIG. 2B shows a sectional view of the pneumostoma management
device of FIG. 2A partially implanted in a pneumostoma.
[0053] FIG. 2C shows a perspective view of a drug delivery device
designed to operate with the pneumostoma management device of FIGS.
2A and 2B according to an embodiment of the present invention.
[0054] FIG. 2D shows a sectional view of the drug delivery device
of FIG. 2C mated with the pneumostoma management device of FIGS. 2A
and 2B according to an embodiment of the present invention.
[0055] FIG. 2E shows a positioning of a pneumostoma management
device and drug delivery device relative to the chest of a
patient.
[0056] FIG. 2F shows steps for using a drug delivery device
according to an embodiment of the present invention.
[0057] FIG. 3A shows a perspective view of an alternative drug
delivery device according to an embodiment of the present
invention.
[0058] FIG. 3B shows a sectional view of the drug delivery device
of FIG. 3A.
[0059] FIGS. 4A and 4B show sectional views of an alternative drug
delivery device according to an embodiment of the present
invention.
[0060] FIG. 5A shows a top view of an alternative drug delivery
device according to an embodiment of the present invention.
[0061] FIG. 5B shows a side view of the drug delivery device of
FIG. 5A.
[0062] FIG. 6 shows a drug delivery device for use in conjunction
with a nebulizer.
[0063] FIGS. 7A and 7B show views of an alternative drug delivery
device according to an embodiment of the present invention.
[0064] FIG. 8A shows a perspective view of a drug delivery device
designed to operate with the pneumostoma management device of FIGS.
2A and 2B according to an alternate embodiment of the present
invention.
[0065] FIG. 8B shows a sectional view of the drug delivery device
of FIG. 8A mated with the pneumostoma management device of FIGS. 2A
and 2B.
[0066] FIG. 8C shows steps for using a drug delivery device such as
shown in FIG. 8A.
[0067] FIGS. 9A and 9B show sectional views of an alternative drug
delivery device according to an embodiment of the present
invention.
[0068] FIG. 10A shows a view of a spirometry system for assessing
the functionality of a pneumostoma according to an embodiment of
the present invention.
[0069] FIG. 10B shows a view of a gas analysis system for assessing
the functionality of a pneumostoma according to an embodiment of
the present invention.
[0070] FIG. 10C shows a view of lung imaging system for imaging gas
diffusion from a pneumostoma according to an embodiment of the
present invention.
[0071] FIGS. 10D and 10E show views of a diagnostic device for
delivering diagnostic gas to a pneumostoma or sampling gas from a
pneumostoma according to embodiments of the present invention.
[0072] FIGS. 11A-11C show views of a pneumostoma management device
which provides a therapeutic agent to the pneumostoma.
[0073] FIGS. 11D and 11E show vies of a pneumostoma management
device having drug infusion features.
DETAILED DESCRIPTION OF THE INVENTION
[0074] The following description is of the best modes presently
contemplated for practicing various embodiments of the present
invention. The description is not to be taken in a limiting sense
but is made merely for the purpose of describing the general
principles of the invention. The scope of the invention should be
ascertained with reference to the claims. In the description of the
invention that follows, like numerals or reference designators will
be used to refer to like parts or elements throughout. In addition,
the first digit of a reference number identifies the drawing in
which the reference number first appears.
Pneumostoma Formation and Anatomy
[0075] FIG. 1A shows the chest of a patient identifying alternative
locations for creating a pneumostoma that may be managed using the
system of the present invention. A first pneumostoma 110 is shown
on the front of the chest 100 over the right lung 101 (shown in
dashed lines). The pneumostoma is preferably positioned over the
third intercostal space on the mid-clavicular line. Thus the
pneumostoma 110 is located on the front of the chest between the
third and fourth ribs. Although the pneumostoma 110 is preferably
located between two ribs, in alternative procedures a pneumostoma
can also be prepared using a minithoracotomy with a rib
resection.
[0076] In FIG. 1A a second pneumostoma 112 is illustrated in a
lateral position entering the left lung 103 (shown in dashed
lines). The pneumostoma 112 is preferably positioned over the
fourth or fifth intercostal space under the left arm 104. In
general, one pneumostoma per lung is created; however, more or less
than one pneumostoma per lung may be created depending upon the
needs of the patient. In most humans, the lobes of the lung are not
completely separate and air may pass between the lobes.
[0077] A pneumostoma is surgically created by forming an artificial
channel through the chest wall and joining that channel with an
opening through the visceral membrane of the lung into parenchymal
tissue of the lung to form an anastomosis. The anastomosis is
joined and sealed by sealing the channel from the pleural cavity
using adhesives, mechanical sealing and/or pleurodesis. Methods for
forming the channel, opening, anastomosis and pleurodesis are
disclosed in applicant's pending and issued patents and
applications including U.S. patent application Ser. No. 10/881,408
entitled "Methods and Devices to Accelerate Wound Healing in
Thoracic Anastomosis Applications," U.S. patent application Ser.
No. 12/030,006 entitled "Variable Parietal/Visceral Pleural
Coupling," and U.S. Provisional Patent Application Ser. No.
61/038,371 entitled "Surgical Procedure And Instrument To Create A
Pneumostoma And Treat Chronic Obstructive Pulmonary Disease" which
are incorporated herein by reference in their entirety.
[0078] FIG. 1B shows a sectional view of chest 100 illustrating the
position of the pneumostoma 110. The parenchymal tissue 132 of the
lung 130 is comprised principally of alveoli 134. The alveoli 134
are the thin walled air-filled sacs in which gas exchange takes
place. Air flows into the lungs through the natural airways
including the trachea 136, carina 137, and bronchi 138. Inside the
lungs, the bronchi branch into a multiplicity of smaller vessels
referred to as bronchioles (not shown). Typically, there are more
than one million bronchioles in each lung. Each bronchiole connects
a cluster of alveoli to the natural airways. As illustrated in FIG.
1B, pneumostoma 110 comprises a channel through the thoracic wall
106 of the chest 100 between two ribs 107. Pneumostoma 110 opens at
an aperture 126 through the skin 114 of chest 100.
[0079] FIG. 1C shows a detailed sectional view of the pneumostoma
110. As illustrated in FIG. 1C, pneumostoma 110 comprises a channel
120 through the thoracic wall 106 of the chest 100 between the ribs
107. The channel 120 is joined to cavity 122 in the parenchymal
tissue 132 of lung 130. An adhesion or pleurodesis 124 surrounds
the channel 120 where it enters the lung 130. The thoracic wall 106
is lined with the parietal membrane 108. The surface of the lung
130 is covered with a continuous sac called the visceral membrane
138. The parietal membrane 108 and visceral membrane 138 are often
referred to collectively as the pleural membranes. Between the
parietal membrane 108 and visceral membrane 138 is the pleural
cavity (pleural space) 140. The pleural cavity usually only
contains a thin film of fluid that serves as a lubricant between
the lungs and the chest wall. In pleurodesis 124 the pleural
membranes are fused and/or adhered to one another eliminating the
space between the pleural membranes in that region.
[0080] An important feature of the pneumostoma is the seal or
adhesion surrounding the channel 120 where it enters the lung 130
which may comprise a pleurodesis 124. Pleurodesis 124 is the fusion
or adhesion of the parietal membrane 108 and visceral membrane 138.
A pleurodesis may be a complete pleurodesis in which the entire
pleural cavity 140 is removed by fusion of the visceral membrane
138 with the parietal membrane 108 over the entire surface of the
lung 130. However, as shown in FIG. 1C, pleurodesis 124 is
preferably localized to the region surrounding the channel 120. The
pleurodesis 124 surrounding the channel 120 prevents air from
entering the pleural cavity 140. If air is permitted to enter
pleural cavity 140, a pneumothorax will result and the lung may
collapse.
[0081] Pleurodesis 124 can be created between the visceral pleura
of the lung and the inner wall of the thoracic cavity using
chemical methods including introducing into the pleural space
irritants such as antibiotics (e.g. Doxycycline or Quinacrine),
antibiotics (e.g. iodopovidone or silver nitrate), anticancer
therapeutic agents (e.g. Bleomycin, Mitoxantrone or Cisplatin),
cytokines (e.g. interferon alpha-2.beta. and Transforming growth
factor-.beta.); pyrogens (e.g. Corynebacterium parvum,
Staphylococcus aureus superantigen or OK432); connective tissue
proteins (e.g. fibrin or collagen) and minerals (e.g. talc slurry).
A pleurodesis can also be created using surgical methods including
pleurectomy. For example, the pleural space may be mechanically
abraded during thoracoscopy or thoracotomy. This procedure is
called dry abrasion pleurodesis. A pleurodesis may also be created
using radiotherapy methods, including radioactive gold or external
radiation. These methods cause an inflammatory response and or
fibrosis, healing, and fusion of the pleural membranes.
Alternatively, a seal can be created in an acute manner between the
pleural membranes using biocompatible glues, meshes or mechanical
means such as clamps, staples, clips and/or sutures. The adhesive
or mechanical seal may develop into pleurodesis over time. A range
of biocompatible glues are available that may be used on the lung,
including light-activatable glues, fibrin glues, cyanoacrylates and
two part polymerizing glues. Applicant's copending U.S. patent
application Ser. No. 12/030,006 entitled "VARIABLE
PARIETAL/VISCERAL PLEURAL COUPLING" discloses methods such as
pleurodesis for coupling a channel through the chest wall to the
inner volume of the lung without causing a pneumothorax and is
incorporated herein by reference for all purposes.
[0082] When formed, pneumostoma 110 provides an extra pathway for
exhaled air to exit the lung 130 reducing residual volume and
intra-thoracic pressure without the air passing through the major
natural airways such as the bronchi 138 and trachea 136. Collateral
ventilation is particularly prevalent in an emphysematous lung
because of the deterioration of lung tissue caused by COPD.
Collateral ventilation is the term given to leakage of air through
the connective tissue between the alveoli 134. Collateral
ventilation may include leakage of air through pathways that
include the interalveolar pores of Kohn, bronchiole-alveolar
communications of Lambert, and interbronchiolar pathways of Martin.
This air typically becomes trapped in the lung and contributes to
hyperinflation. In lungs that have been damaged by COPD and
emphysema, the resistance to flow in collateral channels (not
shown) of the parenchymal tissue 132 is reduced allowing collateral
ventilation to increase. Air from alveoli 134 of parenchymal tissue
132 that passes into collateral pathways of lung 130 is collected
in cavity 122 of pneumostoma 110. Pneumostoma 110 thus makes use of
collateral ventilation to collect air in cavity 122 and vent the
air outside the body via channel 120 reducing residual volume and
intra-thoracic pressure and bypassing the natural airways which
have been impaired by COPD and emphysema.
[0083] By providing this ventilation bypass, the pneumostoma allows
stale air trapped in the parenchymal tissue 132 to escape from the
lung 130. This reduces the residual volume and intra-thoracic
pressure. The lower intra-thoracic pressure reduces the dynamic
collapse of airways during exhalation. By allowing the airways to
remain patent during exhalation, labored breathing (dyspnea) and
residual volume (hyperinflation) are both reduced. Pneumostoma 110
not only provides an extra pathway that allows air to exit the lung
130 but also allows more fresh air to be drawn in through the
natural airways. This increases the effectiveness of all of the
tissues of the lung 130 and improves gas exchange. Pneumostoma 110
thus achieves many of the advantages sought by lung volume
reduction surgery without surgically removing a portion of the lung
or sealing off a portion of the lung.
[0084] U.S. Pat. No. 7,398,782 titled "Pulmonary Drug Delivery" to
Tanaka discusses the local delivery of therapeutic agents directly
into the lungs for treating various disease conditions and is
incorporated herein by reference. As disclosed herein, a
pneumostoma management system in accordance with embodiments of the
present invention is advantageous to maintain the patency of a
pneumostoma and control flow of materials between the exterior of
the patient and the parenchymal tissue of the lung via a
pneumostoma. The pneumostoma management system includes a
pneumostoma management device and a drug delivery device.
Pneumostoma Management System Including Drug Delivery Device
[0085] As described above, a pneumostoma may be created to treat
the symptoms of chronic obstructive pulmonary disease. A patient is
typically provided with a pneumostoma management device to protect
the pneumostoma and keeps the pneumostoma open on a day-to-day
basis. In general terms a pneumostoma management device ("PMD")
comprises a tube which is inserted into the pneumostoma and an
external component which is secured to the skin of the patient to
keep the tube in place. Gases escape from the lung through the tube
and are vented external to the patient. The pneumostoma management
device may, in some, but not all cases, include a filter which only
permits gases to enter or exit the tube. The pneumostoma management
device may, in some, but not all cases, include a one-way valve
which allows gases to exit the lung but not enter the lung through
the tube.
[0086] FIGS. 2A through 2E illustrate views of a pneumostoma
management system including a pneumostoma management device ("PMD")
201 and a drug delivery device 260 in accordance with an embodiment
of the present invention. The drug delivery device 260 is shown in
FIGS. 2C, 2D and 2E. As shown in FIGS. 2A and 2B, PMD 201 includes
a chest mount 202 which may be mounted to the skin of the patient
and a pneumostoma vent 204 which is fitted to the chest mount 202.
In a preferred embodiment pneumostoma vent 204 is mounted through
an aperture 224 in chest mount 202. Chest mount 202 has a first
coupling that engages a second coupling of the pneumostoma vent to
releasably secure the pneumostoma vent 204 to the chest mount 202.
The join between the two components of PMD 201 is engineered to
ensure that pneumostoma vent 204 cannot be over-inserted into the
lung if it separates from chest mount 202. Applicant's related
patent applications referenced above provide further description of
pneumostoma management devices and are incorporated herein by
reference in its entirety.
[0087] Referring now to FIG. 2B, pneumostoma vent 204 includes a
tube 240 sized and configured to fit within the channel of a
pneumostoma 110. Tube 240 is stiff enough that it may be inserted
into a pneumostoma without collapsing. Over time a pneumostoma may
constrict and it is one function of PMD 201 to preserve the patency
of the channel of the pneumostoma by resisting the natural tendency
of the pneumostoma to constrict. Tube 240 of pneumostoma vent 204
preferably comprises an atraumatic tip 252 at the distal end as
shown in FIGS. 2A and 2B. (This application uses the terms proximal
and distal regarding the components of the pneumostoma management
system in the conventional manner. Thus, proximal refers to the end
or side of a device closest to the hand operating the device,
whereas distal refers to the end or side of a device furthest from
the hand operating the device.) Tip 252 may be rounded, beveled or
curved in order to reduce irritation or damage to the tissues of
the pneumostoma or lung during insertion or while in position.
Opening 254 in tip 252 allows the entry of gases from the cavity of
the pneumostoma 110 into lumen 258 of tube 240. Tube 240 is
optionally provided with one or more side openings (not shown)
positioned near tip 252 and/or along the length of tube 240 to
facilitate the flow of gas and/or mucous/discharge into lumen
258.
[0088] Tube 240 of pneumostoma vent 204 is sufficiently long that
it can pass through the thoracic wall and into the cavity of a
pneumostoma inside the lung. Pneumostoma vent 204 is not however so
long that it penetrates so far into the lung that it might cause
injury. The material and thickness of tube 240 of pneumostoma vent
204 is selected such that tube 240 is soft enough that it will
deform rather than cause injury to the pneumostoma or lung.
Pneumostoma vent 204 has an opening 254 in tip 252 of tube 240. The
length of tube 240 required for a pneumostoma vent 204 varies
significantly between different pneumostomas. A longer tube 240 is
usually required in patients with larger amounts of body fat on the
chest. A longer tube 240 is usually required where the pneumostoma
is placed in the lateral position 112 rather than the frontal
position 110. Because of the variation in pneumostomas, pneumostoma
vents 204 are manufactured having tubes 240 in a range of sizes and
a patient is provided with a pneumostoma vent 204 having a tube 240
of appropriate length for the patient's pneumostoma. Tube 240 may
be from 30 to 120 mm in length and from 5 mm to 20 mm in diameter
depending on the size of a pneumostoma. A typical tube 240 may be
between 40 mm and 80 mm in length and between 8 mm and 12 mm in
diameter. In alternative embodiments, a pneumostoma vent 204 is
made with a single length (such as 120 mm) of tube 240 and tube 240
is then cut to the length appropriate for a particular patient.
Where a single length tube 240 is provided and subsequently cut to
length it is desirable that the tube be shaped such that at each of
a plurality of cut points cutting will generate an atraumatic tip.
This can be achieved, for example, by including a series of rounded
narrow points on tube 240.
[0089] Pneumostoma vent 204 includes a cap 242 and a hydrophobic
filter 248 over the opening 255 in the proximal end of tube 240.
Hydrophobic filter 248 is positioned over the proximal opening 255
into lumen 258. Hydrophobic filter 248 is positioned and mounted
such that material moving between lumen 258 and the exterior of
pneumostoma vent 204 must pass through hydrophobic filter 248.
Hydrophobic filter 248 is preferably designed such to fit into a
recess in cap 242. As shown in FIG. 2B, cap 242 comprises a recess
238 into which hydrophobic filter 248 may be fit. Hydrophobic
filter 248 may alternatively be fitted into cap 242 using a joint
such as a threaded coupling or adhesive or, in some cases, formed
integrally with cap 242. Hydrophobic filter 248 may be made from a
material such as medical grade GOR-TEX (W. L. Gore &
Associates, Inc., Flagstaff, Ariz.). As shown in FIG. 2B, a snap
ring 243 locks cap 242 and hydrophobic filter 248 onto the proximal
end of tube 240.
[0090] Hydrophobic filter 248 serves several purposes. In general,
hydrophobic filter 248 controls the passage of solid or liquid
material between the lumen 258 and the exterior of cap 242. For
example, hydrophobic filter 248 prevents the flow of water into the
lumen 258 through proximal opening 255. Thus, a patient using PMD
201 may shower without water entering the lung through the
pneumostoma. Hydrophobic filter 248 may also be selected so as to
prevent the entry of microbes, pollen and other allergens and
pathogens into the lumen 258. Hydrophobic filter 248 also prevents
the exit of liquid and particulate discharge from lumen 258 to the
exterior of pneumostoma vent 204. This is desirable to prevent
contact between liquid and particulate discharge and clothing for
example.
[0091] Chest mount 202 connects to the proximal end of pneumostoma
vent 204. In one embodiment, illustrated in FIGS. 2A and 2B, chest
mount 202 comprises a flange 222 and an aperture 224. The aperture
224 is adapted and configured to receive the pneumostoma vent 204.
Chest mount 202 is designed to have a smooth surface and a low
profile so it is comfortable for the patient to wear. Chest mount
202 should be designed so as not to snag on the patient's clothing
or to restrict motion of the patient's arm (if placed in a lateral
pneumostoma 112). Flange 222 is significantly wider than
pneumostoma vent 204. Flange 222 thus comprises a contact surface
232 which contacts the skin of the patient surrounding the
pneumostoma and positions the aperture 224 over the opening of the
pneumostoma. Flange 222 is designed such that it is sufficiently
flexible that it can conform to the surface of the chest. Contact
surface 232 is also provided with a pad of biocompatible adhesive
234, such as a hydrocolloid adhesive, for securing flange 222 to
the skin of the patient. The adhesive 234 may be protected by a
protector sheet that is removed prior to use of flange 222.
Adhesive 234 should be selected so as to secure flange 222 to the
chest of the patient in the correct position relative to the
pneumostoma without causing undue irritation to the skin of the
patient. The adhesive need not create an air tight seal between
flange 222 and the skin of the patient. Suitable adhesive pads are
available commercially from Avery Dennison (Painesville, Ohio).
[0092] Referring again to FIGS. 2A and 2B, cap 242 is attached to
the proximal end of tube 240. Hydrophobic filter 248 is sandwiched
between cap 242 and tube 240. An opening 244 in cap 242
communicates with the lumen 258 of tube 240 via hydrophobic filter
248. As shown in FIGS. 2A and 2B, cap 242 comprises a lip 246 which
releasably engages lip 227 of recess 226 of flange 222 to secure
pneumostoma vent 204 within the recess 226 of flange 222. Lip 246
forms a coupling element of pneumostoma vent 204 that cooperates
with recess 226 to releasably secure pneumostoma vent 204 into
chest mount 202 with tube 240 positioned through aperture 224.
[0093] Referring again to FIGS. 2A and 2B, flange 222 is generally
circular but is provided with one or more tabs 236 to facilitate
application and removal of flange 222 from the skin of the patient.
Chest mount 202 comprises an aperture 224 through which tube 240 of
pneumostoma vent 204 may be inserted. Flange 222 is slightly convex
on the upper surface 235. Flange 222 includes a recess 226 into
which cap 242 of pneumostoma vent 204 may be press fit. Flange 222
is thick enough in the region of aperture 224 to receive the cap
242 of pneumostoma vent 204 so that the cap of pneumostoma vent 204
is flush with the upper surface 235 of flange 222. Recess 226 forms
a coupling adapted to releasably secure the cap 242 of pneumostoma
vent 204 into flange 222. Recess 226 has a lip 227 to releasably
secure the cap 242 of pneumostoma vent 204 into flange 222.
However, other couplings may be used to releasably secure
pneumostoma vent 204 to chest mount 202 including clips, pins,
snaps, catches, threaded joints, temporary adhesive and the
like.
[0094] In a preferred embodiment, an aperture plate 228 is embedded
in the conformable polymer of flange 222. The aperture plate 228
defines aperture 224 of chest mount 202. Aperture plate 228 is made
of a stiffer, less compliant material than flange 222 in order that
the dimensions of aperture 224 are tightly controlled. Aperture
plate 228 is stiff enough that the size and shape of aperture 224
remains stable even under any reasonably possible application of
force to chest mount 202. It should be noted that the outer
diameter of each of snap ring 243, hydrophobic filter 248, flange
241 and cap 242 is larger than the diameter of aperture 224 of
aperture plate 228. Thus, snap ring 243, hydrophobic filter 248,
flange 241 and cap 242 cannot pass through aperture 224 into the
pneumostoma 110. Distal tip 252 of tube 240 and the body of tube
240 are small enough to pass through aperture 224 however, flange
241 and/or cap 242 serve to limit the passage of tube 240 through
aperture 224. These safety features prevent unsafe entry of any of
the components of pneumostoma vent 204 into pneumostoma even in the
unlikely event of damage to the device. Likewise all the components
of the chest mount 202 such as flange 222 and aperture plate 224
are significantly larger than the aperture of a pneumostoma thus
precluding passage of any component of the chest mount 202 into a
pneumostoma even in the unlikely event of damage to the device.
[0095] Referring now to FIGS. 2C and 2D which show views of a drug
delivery device 260 designed to be used in conjunction with PMD 201
of FIGS. 2A and 2B as part of a pneumostoma management system. FIG.
2C shows a perspective view of drug delivery device 260. FIG. 2D
shows a sectional view through drug delivery device 260 of FIG. 2C
when mounted in a chest mount 202. As shown in FIGS. 2C and 2D,
drug delivery device 260 includes a therapeutic agent dispenser
262, a coupling 264 and a tube 266. Drug delivery device 260 is
configured such that tube 266 may be inserted through aperture 224
of chest mount 202 into pneumostoma 110. Tube 266 is sufficiently
long to enter the pneumostoma but is not so long that it might
cause injury to the pneumostoma. Coupling 264 is designed such that
it is too large to pass through aperture 224 of chest mount 202
thereby preventing further insertion of tube 266 into pneumostoma
110. Coupling 264 may optionally be provided with a feature such as
a lip 265 for releasably engaging lip 227 of recess 228 of chest
mount 202. A range of drug delivery devices may be manufactured
each having a size appropriate for a different pneumostoma.
[0096] To simplify manufacture, drug delivery device 260 may be
designed to use some components in common with pneumostoma vent
240. For example, the range of tubes 240 of the pneumostoma vent
may be used as tube 266 of drug delivery device 260. Alternatively
it may be preferable to make drug delivery device with only one
size of tube 266 and thus the shortest of tubes 240 may be selected
for use in drug delivery device 260. In some embodiments, the snap
ring 243 may also be a shared component 264. The distal end of
coupling 264 is shaped similarly to cap 242 and thus the snap ring
243 can join tube 266 to coupling 264 in the same manner as tube
240 is coupled to cap 242. Also the exterior surface of the distal
end of coupling 264 engages chest mount 202 in the same way as cap
242. This simplifies the manufacturing and regulatory process for
drug delivery device 260.
[0097] Therapeutic agent dispenser 262 includes a mechanism for
providing an aerosol, mist or powder in suspended in a propellant
gas under sufficient positive pressure to enter the lung through
the tube. The therapeutic agent dispenser preferably provides
positive pressure to push the therapeutic agent into the
pneumostoma. Suitable therapeutic agent dispenser mechanisms for
providing metered doses of therapeutic agents in a propellant gas
are known. Suitable therapeutic agent dispensers include
therapeutic agent dispensing mechanisms found in nebulizers,
ultrasonic nebulizers, metered dose inhalers and dry powder
inhalers. Dry powder therapeutic agent dispensers deliver a fine
microcrystalline suspension of therapeutic agent. In the example
shown in FIGS. 2C, 2D a pressurized canister 268 is received in
sleeve 270. The outlet valve 269 of canister 268 engages a fixture
272 in the bottom of sleeve 270. When the user pushes canister 268
down into sleeve 270, fixture 272 activates valve 269 to release a
metered dose of therapeutic agent in a propellant gas. The
therapeutic agent and propellant gas pass through a channel 274 in
fixture 270 and are ejected into and through tube 266 as shown by
arrow 276.
[0098] Note that in some embodiments it is unnecessary for
therapeutic agent dispenser 262 to provide a propellant gas at
positive pressure to introduce the aerosol, mist or powder into the
lung through the pneumostoma. In some embodiments the therapeutic
agent dispenser 262 provides the therapeutic agent/gas mixture at
or near ambient pressure. Reduced pressure in the pneumostoma
during inhalation by the patient creates a pressure differential
which sucks the therapeutic agent suspended in air/gas into the
pneumostoma.
[0099] FIG. 2E illustrates the positioning of drug delivery device
260 over pneumostoma 112 of FIG. 1A. In a preferred embodiment, the
chest mount 202 remains attached for up to a week thereby avoiding
irritation of the skin caused by daily attachment and removal of a
mount. Chest mount may be positioned by the patient by manual
alignment of the aperture 224 of chest mount 202 with the aperture
of the pneumostoma 112. To use drug delivery device 260, chest
mount 202 is first positioned over a pneumostoma and secured with
adhesive to the skin of the patient. Alternatively a pneumostoma
vent or an alignment tool may be used to align the chest mount.
Drug delivery device 260 is then inserted through the aperture in
the chest mount until it engages the chest mount 202. As shown in
FIG. 2E, the drug delivery device 260 is inserted through chest
mount 202 after pneumostoma vent 204 has been removed. Drug
delivery device 260 is then operated to supply the aerosolized or
dry powder therapeutic agent directly to the parenchymal tissue of
the lung through pneumostoma 112 by operation of therapeutic agent
dispenser 262 either by the patient, caregiver or medical
practitioner.
[0100] FIG. 2F shows an example of a method of using a drug
delivery device according to embodiments of the present invention.
The method may be described in instructions for use provided to the
patient with the drug delivery device. At step 280, the patient
adjusts the pneumostoma management device. Depending on the
operation of the drug delivery device, this step may involve, for
example, removing a component of the pneumostoma vent such as the
filter; removing the entire pneumostoma vent; or removing the
entire pneumostoma management device. At step 282, the patient
positions the drug delivery device in the pneumostoma. In some
embodiments this step will involve connecting the pneumostoma
management device to a tube already positioned in the pneumostoma.
At step 484, the patient loads a dose of the therapeutic agent into
the drug delivery device. In some cases, the therapeutic agent is
provided in single dose containers and thus this will involve
loading a single dose package or indexing a package containing
multiple singe dose containers to a full container. In other cases,
the therapeutic agent will be in a multiple-use container, such as
a pressurized metered dose canister and it will be unnecessary for
the patient to load a therapeutic agent dose unless the container
is empty. The drug delivery device is now prepared for
operation.
[0101] In a typical therapeutic agent delivery operation the
patient will first exhale through the nose/mouth at step 285
immediately prior to actuating the drug delivery device. At step
286 the drug delivery device is actuated to mix the therapeutic
agents (aerosol, gas or dry powder) in the propellant/air. In some
embodiments this mixing step requires a relatively high air
speed/pressure. It may be undesirable for this airspeed/pressure to
be applied to the pneumostoma and thus the location of mixing step
286 may be separated by features to reduce the airspeed/pressure
distance before the mixture reaches the pneumostoma. Such features
may include, for example, space, volume, baffles and the like. At
step 288 application of positive pressure is used to propel the
mixture of therapeutic agent and propellant into the pneumostoma
and/or through the pneumostoma into the lung. The positive pressure
applied at this step may be substantially less than the pressure
used at step 286. The positive pressure may be supplied by a
different mechanism or by a modulation of the same mechanism. Steps
286 and 288 may be combined in one step for example where the
pressure is modulated by the mechanics of the device such that a
higher local pressure is available in one part of the device to mix
the agent but is reduced by the time it reaches the pneumostoma.
Note that in some embodiments it is unnecessary for the therapeutic
agent dispenser to provide propellant gas at positive pressure to
introduce the aerosol, mist or powder into the lung through the
pneumostoma. In some embodiments the drug delivery device remains
at or near ambient pressure and reduced pressure in the pneumostoma
during inhalation by the patient creates a pressure differential
which sucks the aerosol, mist or powder suspended in air/gas into
the pneumostoma.
[0102] At step 290, air is introduced through the pneumostoma to
aid distribution of the therapeutic agent through the lung tissue
by collateral ventilation. Step 290 is optional and may in some
cases be combined with step 288. In some cases step 290 may be
achieved by the patient "inhaling" through the pneumostoma in which
the patient expands the ribcage thereby creating a negative
pressure in the chest to draw air in through the pneumostoma. In
some circumstances this "inhalation" through the pneumostoma may be
enhanced by obstructing the nose and mouth while expanding the
ribcage. However, step 290 may not be necessary and a therapeutic
agent may be efficiently distributed from the pneumostoma through
parenchymal tissue of the lung by collateral ventilation without
the need for additional intake of air through the pneumostoma.
[0103] At step 292, the patient optionally holds their breath for a
time prior to exhaling, such as 10 to 15 seconds. This step may not
be necessary for therapeutic agents delivered into the pneumostoma.
Because the therapeutic agent was not delivered through the natural
airways, it will not be rapidly exhaled through the natural
airways. Indeed, in some cases breathing normally (while
obstructing the pneumostoma) while cause rapid distribution of the
therapeutic agent through the lung with little loss of therapeutic
agent due to exhalation. In some case it may be advantageous to
provide a slight positive pressure of air to the pneumostoma after
delivery of the therapeutic agent to promote diffusion of the
therapeutic agent through the lung. Steps 284 and 292 may be
repeated a number of times if necessary to deliver multiple doses
of therapeutic agent as shown by dashed arrow 294.
[0104] It may be desirable to leave the drug delivery device in
place for a period after delivery of therapeutic agent to prevent
the agent from being ejected through the pneumostoma. After the
therapeutic agent has been delivered, the drug delivery device is
removed from the pneumostoma at step 296. In some cases the drug
delivery device may be detached from the pneumostoma vent of chest
mount. At step 298, the pneumostoma management device is replaced
into the pneumostoma. Alternatively, any removed components of the
pneumostoma management device are reattached. Any or all of the
above steps may be performed and/or controlled by a physician or
caregiver instead of the patient. The therapeutic agent delivery
steps may be repeated according to a particular dosing schedule or
as needed depending on the therapeutic agent and/or physician's
instructions.
Therapeutic Agents For Delivery Through A Pneumostoma
[0105] The present invention provides a drug delivery device which
delivers a therapeutic agent into the lung 130 without passing
through the mouth and the major natural airways such as the bronchi
138 and trachea 136. For inhaled therapeutic agents, a significant
fraction of the therapeutic agent may be deposited in the upper
respiratory tract and may cause unwanted side effects. For example,
inhalation of corticosteroids to reduce inflammation, can suppress
the immune system in the mouth leading to infections. Additionally,
the amount of therapeutic agent reaching the lung can vary
depending upon the abilities of the patient to use the inhaler. In
the present invention a much larger fraction of the therapeutic
agent is delivered directly to the lung. Moreover, the therapeutic
agent is circulated in the lung, at least in part, using collateral
ventilation through the connective tissue between the alveoli 134.
Collateral ventilation is particularly prevalent in an
emphysematous lung because of the deterioration of lung tissue
caused by COPD. Collateral ventilation may distribute the
therapeutic agent through pathways that include the interalveolar
pores of Kohn, bronchiole-alveolar communications of Lambert, and
interbronchiolar pathways of Martin. This may provide better and/or
more direct access to the damaged tissues of the lung than is
possible through the natural airways.
[0106] The dosage of a particular therapeutic agent required to be
delivered by the pneumostoma will, in many cases, be significantly
less than the dosage that would be required to be delivered by the
natural airways for the same therapeutic effect. The lower dose can
be used because the therapeutic agent delivered through the
pneumostoma is not trapped in the natural airways by the body's
natural defenses against particulates in the air. Not only does a
higher fraction of therapeutic agent reach the lung tissue but the
variability of drug delivery is also less. The lower dosage
required for delivery through the pneumostoma is advantageous as it
reduces the amount and therefore cost of the therapeutic agent,
reduces side effects to the patient, and renders dosing more
consistent.
[0107] As used herein, therapeutic agents may be solid, liquid
(including solutions and suspensions), and/or gas. In general,
there are three types of therapeutic agents that may be delivered
using the methods and devices of the present invention: therapeutic
agents to treat the tissues of the pneumostoma; therapeutic agents
to treat tissue within the lung; and therapeutic agents to treat
diseases that are not lung-specific.
[0108] For treatment of the pneumostoma, the therapeutic agent has
the shortest distance to travel. The therapeutic agent is
distributed utilizing absorption and diffusion through the
pneumostoma and into lung parenchymal tissue adjacent the
pneumostoma. Parameters of the delivery may be selected so that the
therapeutic agent is selectively absorbed in the immediate vicinity
of the pneumostoma. For example, the droplet/powder size may be
increased and/or the amount of propellant decreased to reduce
transport of the agent away from the pneumostoma. Therapeutic
agents for treating the pneumostoma may include, without
limitation, agents to promote healing, agents to reduce scarring,
agents to maintain the patency of the pneumostoma; agents to
prevent infection; agents to maintain the collateral ventilation
into/from the pneumostoma. Suitable therapeutic agents may have an
anti-inflammatory and/or antiproliferative and/or spasmolytic
and/or endothelium-forming effect, so that the functionality of the
pneumostoma is maintained. Suitable therapeutic agents may include,
for example, steroidal compounds; antibiotics and retinoic
acid.
[0109] For treatment of the tissue within the lung, the therapeutic
agent is distributed utilizing collateral ventilation, absorption
and diffusion through the lung tissues. Parameters of the delivery
may be selected so that the therapeutic agent is readily
transported via collateral channels. For example, the
droplet/powder size may be decreased and/or the amount of
propellant increased to enhance transport of the agent through
collateral channels. The therapeutic agents can include agents
which work directly on the bronchiole mucosa and smooth muscle when
used properly. For example bronchospasm is a major component COPD
which limits airflow. Bronchospasm can be relieved by
bronchodilator therapeutic agent including, without limitation,
beta-2 adrenergic agonists and anti-cholinergic therapeutic agents.
The following therapeutic agents may be particularly suitable as
they are commonly used for treatment of COPD: albuterol, chromolyn,
salbuterol, metaproterenol, pirbuterol, salmeterol, formoterol,
ipratropium, tiotropium, flucatisone, budesonide, flunisolide,
beclamethasone, triamcinolone, mometasone or combinations and
analogs thereof.
[0110] Other agents suitable for treating the lung tissue include,
without limitation: anti-proliferative/antimitotic agents including
natural products such as vinca alkaloids (i.e. vinblastine,
vincristine, and vinorelbine), paclitaxel, epidipodophyllotoxins
(i.e. etoposide, teniposide), antibiotics (dactinomycin
(actinomycin D) daunorubicin, doxorubicin and idarubicin),
anthracyclines, mitoxantrone, bleomycins, plicamycin (mithramycin)
and mitomycin, enzymes (L-asparaginase which systemically
metabolizes L-asparagine and deprives cells which do not have the
capacity to synthesize their own asparagine); antiplatelet agents
such as G(GP) llb/llla inhibitors and vitronectin receptor
antagonists; anti-proliferative/antimitotic alkylating agents such
as nitrogen mustards (mechlorethamine, cyclophosphamide and
analogs, melphalan, chlorambucil), ethylenimines and
methylmelamines (hexamethylmelamine and thiotepa), alkyl
sulfonates-busulfan, nirtosoureas (carmustine (BCNU) and analogs,
streptozocin), trazenes-dacarbazinine (DTIC);
anti-proliferative/antimitotic antimetabolites such as folic acid
analogs (methotrexate), pyrimidine analogs (fluorouracil,
floxuridine, and cytarabine), purine analogs and related inhibitors
(mercaptopurine, thioguanine, pentostatin and
2-chlorodeoxyadenosine {cladribine}); platinum coordination
complexes (cisplatin, carboplatin), procarbazine, hydroxyurea,
mitotane, aminoglutethimide; hormones (i.e. estrogen);
anti-coagulants (heparin, synthetic heparin salts and other
inhibitors of thrombin); fibrinolytic agents (such as tissue
plasminogen activator, streptokinase and urokinase), aspirin,
dipyridamole, ticlopidine, clopidogrel, abciximab; antimigratory;
antisecretory (breveldin); anti-inflammatory: such as
adrenocortical steroids (cortisol, cortisone, fludrocortisone,
prednisone, prednisolone, 6a-methylprednisolone, triamcinolone,
betamethasone, and dexamethasone), non-steroidal agents (salicylic
acid derivatives i.e. aspirin; para-aminophenol derivatives i.e.
acetaminophen; indole and indene acetic acids (inaperturethacin,
sulindac, and etodalac), heteroaryl acetic acids (tolmetin,
diclofenac, and ketorolac), arylpropionic acids (ibuprofen and
derivatives), anthranilic acids (mefenamic acid, and meclofenamic
acid), enolic acids (piroxicam, tenoxicam, phenylbutazone, and
oxyphenthatrazone), anti-asthmatics, nabumetone, gold compounds
(auranofin, aurothioglucose, gold sodium thiomalate);
immunosuppressives: (cyclosporine, tacrolimus (FK-506), sirolimus
(rapamycin), azathioprine, mycophenolate mofetil); angiogenic
agents: vascular endothelial growth factor (VEGF), fibroblast
growth factor (FGF); angiotensin receptor blockers; nitric oxide
donors; antisense oligionucleotides and combinations thereof, cell
cycle inhibitors, mTOR inhibitors, and growth factor receptor
signal transduction kinase inhibitors; retenoids; cyclin/CDK
inhibitors; HMG co-enzyme reductase inhibitors (statins); silver
compound and protease inhibitors.
[0111] The method and devices of the present invention are also
useful for delivery of therapeutic agents for treating diseases
which are not lung-specific. In such cases, the pneumostoma and
lung tissue are utilized as absorption surfaces through which the
agent may enter the blood stream for systemic distribution to all
of the tissues of the body. Parameters of the delivery may be
selected so that the therapeutic agent is readily transported via
collateral channels in order to be absorbed over a large surface
area additionally, the therapeutic agent should be selected/treated
such that it may readily pass into the bloodstream. In one example,
insulin may be delivered to the patient through the pneumostoma.
The insulin is absorbed within the lung and passes into the blood
where it is effective to control blood sugar levels. The insulin
delivery should be more rapid and reliable than inhaled or oral
insulin delivery methods and avoid the need for injection of
insulin.
[0112] Other suitable pharmaceutically-active substances for
delivery through the pneumostoma include, without limitation: amino
acids, anabolics, analgesics and antagonists, anaesthetics,
anti-adrenergic agents, anti-atherosclerotics, antibacterials,
anticholesterolics, anti-coagulants, antidepressants, antidotes,
anti-emetics, anti-epileptic therapeutic agents,
anti-fibrinolytics, anti-inflammatory agents, antihypertensives,
antimetabolites, antimigraine agents, antimycotics, antinauseants,
antineoplastics, anti-obesity agents, antiprotozoals,
antipsychotics, antirheumatics, antiseptics, antivertigo agents,
antivirals, appetite stimulants, bacterial vaccines, bioflavonoids,
calcium channel blockers, capillary stabilizing agents, coagulants,
corticosteroids, detoxifying agents for cytostatic treatment,
diagnostic agents (like contrast media, radiopaque agents and
radioisotopes), electrolytes, enzymes, enzyme inhibitors, ferments,
ferment inhibitors, gangliosides and ganglioside derivatives,
hemostatics, hormones, hormone antagonists, hypnotics,
immunomodulators, insulin, immunostimulants, immunosuppressants,
minerals, muscle relaxants, neuromodulators, neurotransmitters and
neurotrophins, osmotic diuretics, parasympatholytics,
para-sympathomimetics, peptides, proteins, psychostimulants,
respiratory stimulants, sedatives, serum lipid reducing agents,
smooth muscle relaxants, sympatholytics, sympathomimetics,
vasodilators, vasoprotectives, vectors for gene therapy, viral
vaccines, viruses, vitamins, oligonucleotides and derivatives,
saccharides, polysaccharides, glycoproteins, hyaluronic acid, and
any excipient that can be used to stabilize a proteinaceous
therapeutic.
[0113] The therapeutic agent dosage will depend upon factors
including: the intended location of action of therapeutic agent,
the efficiency of distribution of the therapeutic agent, the
repeatability of distribution of the therapeutic agent and the
amount/concentration of therapeutic agent necessary for therapeutic
action. In general the dosage will be first determined during
trials of the therapeutic agent on a population. Based upon trials,
the physician will determine a dose for a particular patient and
prescribe the therapeutic agent and/or delivery protocol
accordingly. For example a physician may prescribe larger sized
doses of therapeutic agent or a larger number of repetitions of
dosages to achieve the same total dosage. Therapeutic agent
delivery through the pneumostoma requires therapeutic agents to
travel a shorter pathway than inhaled therapeutic agent leading to
more efficient and repeatable distribution. Additionally, the
therapeutic agent is not subject to breakdown by stomach acid and
enzymes as it is when delivered via the oral route. The increased
efficiency and repeatability of distribution means that, in
general, less therapeutic agent need be included per dose,
enhancing control of the therapeutic effects and reducing
side-effects.
Propellants For Delivery of Therapeutic Agents Through A
Pneumostoma
[0114] In the past, chlorofluorocarbons were the primary substances
used as propellants in aerosols. Since 1978, the use of
chlorofluorocarbon-emitting products in the United States has been
curtailed sharply because of their adverse effects upon the ozone
layer. The pharmaceutical industry has developed alternative
propellants such as hydro-fluoroalkanes which are the new
environmentally-friendly chemical propellants. Both
chlorofluorocarbons and hydro-fluoroalkanes are suitable chemical
propellants for use in the present invention.
[0115] Lower pressures and flow rates are required for direct
delivery of therapeutic agents to the lung in embodiments of the
present invention than are needed for delivery via inhalation. This
allows for the use of air at slight positive pressures to be used
to propel the therapeutic agent a short distance into the lung. As
used herein propellant should be taken to include chemical
propellants as well as gases at positive pressure. The air may be
provided by a fan, pump, cylinder or bag, for example which may be
operated by a powered actuator or manually. The pressure of
propellant supplied by the device should be carefully
controlled/regulated to ensure that it does not damage the
pneumostoma or lung tissue. In some cases, a safety valve may be
provided to allow gas to escape the pneumostoma or drug delivery
device if the pressure supplied to the pneumostoma exceeds a safe
threshold. Note that in some embodiments the drug delivery device
remains at or near ambient pressure and reduced pressure in the
pneumostoma during inhalation by the patient creates a positive
pressure differential which sucks the aerosol, mist or powder
suspended in air/gas into the pneumostoma.
Diagnostic Agents For Delivery Through A Pneumostoma
[0116] In alternative embodiments, a diagnostic agent rather than a
therapeutic agent may be delivered through the pneumostoma. The
diagnostic agent may be useful for diagnosing lung function in
general and pneumostoma function in particular. For example,
polarized Helium-3 may be utilized to enhance nuclear magnetic
resonance/magnetic resonance imaging of the lung (analogous to the
way contrast agents enhance X-ray imaging). Polarized helium-3 may
be produced with lasers and the magnetized pressurized gas may be
stored for several days. When inhaled, the gas can be imaged with
an MRI-like scanner which produces breath by breath images of lung
ventilation, in real-time. Polarized helium-3 may thus, be used to
visualize airways in static or dynamic fashion. Introducing a
controlled amount of Helium-3 through the pneumostoma and imaging
the diffusion of Helium-3 into the lung over time may be utilized
to evaluate the function of the pneumostoma and the prevalence of
collateral ventilation pathways connecting the pneumostoma to the
remainder of the lung. Such evaluation may be useful in determining
the location and/or desirability of additional pneumostomas. A
source of polarized Helium-3 may be connected to the PMD and/or
pneumostoma using one of the several techniques and mechanism
described herein.
[0117] In an alternative method, a diagnostic gas is introduced
through the pneumostoma and the gas is measured as it is exhaled
through the natural airways. The diagnostic gas may for example be
a gas mixture such as DLCO gas used in diffusion spirometry (which
nominally consists of 10% helium, 3000 ppm carbon monoxide and the
balance air). The difference between gas concentrations in the gas
introduced through the pneumostoma and exhaled by the patient is
measured and factored with inspired gas volume and other parameters
to calculate factors related to collateral ventilation and
pneumostoma function. During exhalation, a portion of the breath is
collected in a sample collection system and then assessed using a
helium sensor, gas chromatograph. The time course of exhalation of
the diagnostic gas is indicative of factors such as pneumostoma
functionality and collateral ventilation without the need for
magnetic resonance imaging.
Alternative Drug Delivery Devices
[0118] FIGS. 3A and 3B show an alternative drug delivery device to
deliver therapeutic agents to a pneumostoma. FIG. 3A shows a
perspective view of an alternative drug delivery device 310. FIG.
3B shows a sectional view of the drug delivery device 310. As shown
in FIGS. 3A and 3B, drug delivery device 310 includes a therapeutic
agent dispenser 312 attached to a flange 314 which is attached to a
tube 316. Flange 314 is significantly larger than the diameter of
tube 316. Flange 314 is too large to enter a pneumostoma and thus
acts as a stop to prevent further insertion of tube 316 when flange
314 makes contact with the skin of the patient's chest. The contact
surface 315 of flange 314 may also be used to make a temporary seal
surrounding the pneumostoma so that when applying therapeutic agent
delivery to the pneumostoma there is reduced leakage of
propellant/therapeutic agent around tube 316. Contact surface 315
and/or tube 316 may be provided with surface features to enhance
the formation of a temporary seal between flange 314 and the skin
of the chest. An annular ridge 318 is shown in FIG. 3B.
[0119] Tube 316 extends far enough past flange 314 that it can pass
through the thoracic wall and into the pneumostoma. Tube 316 is not
however so long that it may cause injury to the pneumostoma or
lung. The length of a pneumostoma varies significantly between
different patients. A longer tube 316 may be desirable for a longer
pneumostoma. Because of the variation in pneumostomas, drug
delivery devices 310 may be manufactured having tubes 316 in a
range of sizes. A patient may then be provided with a drug delivery
device 310 having a tube 316 of appropriate length for the
patient's pneumostoma. Tubes 316 may be from 30 to 120 mm in length
and from 5 mm to 20 mm in diameter depending on the size of a
pneumostoma. A typical tube 240 may be between 40 mm and 80 mm in
length and between 8 mm and 12 mm in diameter. In alternative
embodiments a drug delivery device may be made with a tube 316 of a
single length (such as 120 mm) which is then cut to the length
appropriate for a particular patient. Alternatively a fixed short
tube may be used for all patients--such a tube will occupy at least
the entrance to the pneumostoma and therefore suffice for the
delivery of the therapeutic agent. Tube 316 of drug delivery device
310 preferably has an atraumatic tip 317 at the distal end to
prevent injury and/or irritation to the pneumostoma during
insertion.
[0120] As shown in FIGS. 3A and 3B, flange 314 and tube 316 of drug
delivery device 310 are made in one piece and permanently attached
to therapeutic agent dispenser 312. A join is shown between
therapeutic agent dispenser 312 and flange 314 because it is
preferred that a stiffer material be used for therapeutic agent
dispenser 312 and a more flexible material be used for tube 316
which enter the pneumostoma. The parts may be formed separately and
then joined by welding, gluing or otherwise bonding/connecting.
Note that, for safety reasons, each of the components of
therapeutic agent dispenser is preferably too large to fit through
tube 316. This prevents aspiration of any of the components into
the lung even in the event of damage to drug delivery device 310.
As shown in FIG. and 3B a pressurized canister 368 is received in
sleeve 370. The outlet valve 369 of canister 368 engages a fixture
372 in the bottom of sleeve 370. When the user pushes canister 368
down into sleeve 370, fixture 372 activates valve 369 to release a
metered dose of therapeutic agent in a propellant gas. The
therapeutic agent and gas passes through a channel 374 in fixture
372 and are ejected into and through tube 316 as shown by arrow
376.
[0121] FIGS. 4A and 4B show an alternative drug delivery device 410
to supply a therapeutic agent in/through a pneumostoma. The drug
delivery device 410 operates in conjunction with a pneumostoma
management device (PMD) 440 located within a pneumostoma 110. In
the PMD 440 of FIGS. 4A and 4B, tube 442 is formed in one piece
with (or permanently attached to) a flange 444. PMD 440 has a
hydrophobic filter 446 press fit into the proximal end of tube 442
and has a biocompatible adhesive 448 on the contact surface 449 of
flange 444 for releasably securing flange 444 to the skin 114 of
the patient's chest 100. As shown in FIG. 4D, drug delivery device
410 has a mating section 412, having a mating surface 414 designed
to mate and make a temporary seal with the exterior surface of
flange 444.
[0122] Drug delivery device 440 is utilized with PMD 440 while the
tube 442 of PMD 440 is within pneumostoma 110. As shown in FIG. 4A,
to use drug delivery device 410, hydrophobic filter 446 is first
removed by pulling on tab 450. Mating surface 414 of mating section
412 is then placed against flange 444. In this embodiment, mating
section 412 fits in the space left by the removal of hydrophobic
filter 446 as shown in FIG. 4B. When mating section 412 has formed
a temporary seal with flange 444, therapeutic agent dispenser 416
is operated to dispense the therapeutic agent through the tube 442
of PMD 440 into the pneumostoma 110. After dispensing the
therapeutic agent, the drug delivery device 410 is removed and the
hydrophobic filter 446 is press fit into the proximal end of the
tube 442. Alternatively PMD 440 may be replaced with a new PMD
440.
[0123] FIGS. 5A and 5B show an alternative drug delivery device 510
to supply a therapeutic agent in/through a pneumostoma. FIG. 5A is
a top down view of drug delivery device 510 and FIG. 5B is a side
view of the same device. The drug delivery device 510 is a dry
powder drug delivery device. The therapeutic agent 500 in finely
ground microcrystalline form is stored in a circular blister pack
512. One dose of therapeutic agent 500 is located in each blister
516. In some cases the blister pack 512 may be removed and replaced
in other cases, drug delivery device 510 is discarded after all the
doses in one blister pack have been used.
[0124] As shown in FIGS. 5A and 5B drug delivery device 510
includes a body 520 which receives blister pack 512. Blister pack
512 is supported such that it can rotate in body 520 and index one
blister 516 at a time to a dispensing position within body 520.
Body 520 also carriers a manual actuator 522 on the upper surface
which operates a pumping mechanism 524 to force air into reservoir
526. Pumping mechanism 524 is pressure limited so that the maximum
pressure of air in reservoir 526 is capped at a safe limit.
Reservoir 526 (and/or tube 542) may also be provided with a safety
valve to release any excess pressure. Body 520 has a front surface
528 for making contact with the skin of the patient surrounding the
pneumostoma and limiting insertion of tube 530 to a safe depth. The
size of tube 540 is selected so as to fit in the pneumostoma
without causing injury. Tube 530 has an atraumatic tip 532 at its
distal end and an opening 533 through which the therapeutic agent
is delivered into the pneumostoma. Two trigger buttons 534, 536
protrude from front surface 528 of body 520. The trigger buttons
are connected by a linkage 538 to a valve 540 of reservoir 524.
[0125] To operate drug delivery device 510 the patient depresses
the manual actuator 522 one or more times. A pressure sensitive
indicator (for example venting of a relief valve) indicates when
sufficient pressure has been achieved. Tube 530 is then pushed into
the pneumostoma. When tube 530 is introduced into the pneumostoma,
the trigger buttons 534 and 536 contact the skin of the patient
surrounding the pneumostoma. When slight pressure is applied to
both trigger buttons 534, 536, linkage 538 opens valve 540 and the
air in reservoir 524 escapes via tube 542 over a blister 516
containing the therapeutic agent. One or more baffles 544 is
provided to provide turbulence to ensure that all of the
microcrystalline therapeutic agent is picked up and distributed in
the stream of air and pushed through tube 530 and out of opening
533 into the pneumostoma. In alternative embodiments, a manually
operable trigger may be provided instead of trigger button 534 or
536.
[0126] Drug delivery device 510 is illustrative of an alterative
therapeutic agent dispenser system which does not require a
cylinder of compressed gas or propellant but instead depends on
pumping action by the patient. Additionally, trigger buttons 534
and 536 fire drug delivery device 510 automatically when the
correct position in the pneumostoma is reached. Drug delivery
device 510 has an integrated tube and insertion stop. However, in
alternative embodiments, the dry powder therapeutic agent
dispensing mechanism of FIGS. 5A, 5B may be incorporated in the
other drug delivery devices discussed herein.
[0127] FIG. 6 shows an example of a drug delivery device 610 in the
form of an adapter for coupling a nebulizer 600 to a chest mount
202 in order to introduce a therapeutic agent 602 into a
pneumostoma 110. Nebulizer 600 is a device used to administer
medication to people in the form of a vapor/mist. Nebulizer 600
pumps air or oxygen through a liquid therapeutic agent 602 (which
may be liquid compound or a solution or suspension of a therapeutic
agent in a carrier liquid) to turn it into a vapor/mist 604, which
is then introduced to the patient via pneumostoma 110.
Alternatively the nebulizer produces the vapor/mist ultrasonically
or using a vibrating micro-mesh. As shown in FIG. 6, nebulizer 600
provides a vapor/mist 604 of therapeutic agent 602 under a
regulated low positive pressure through conduit 606 to drug
delivery device 610. Drug delivery device 610 includes a tube 616
which enters pneumostoma 610. At the proximal end of tube 616 is a
coupling 618 which engages chest mount 202 to releasably secure
drug delivery device 610 to chest mount 202 and within pneumostoma
110 while preventing over-insertion of tube 616. In alternative
embodiments drug delivery device 610 may be integrated with a
flange which engages the chest of the patient surrounding the
pneumostoma directly to releasably secure the drug delivery device
to the chest the patient and prevent over insertion of tube
616.
[0128] Nebulizers such as nebulizer 600 of FIG. 6 are typically
plug-in devices that the patient may use for home treatment. In
use, the patient would typically remove the pneumostoma vent from
the chest mount 202 and insert the drug delivery device 610
connected to nebulizer 600. Typically a specific amount of a
therapeutic agent is mixed with a specific volume of sterile water
or saline and loaded into the nebulizer. The patient would then
operate the nebulizer to provide the dose of therapeutic agent for
a desired period of time or until the entire dose is delivered. The
patient continues to breathe normally during this process. As the
patient breathes, the therapeutic agent will be supplied via
pneumostoma 110 into the parenchymal tissue of the lung. The
therapeutic agent will then be dispersed efficiently throughout the
lung by the process of collateral ventilation. Collateral
ventilation is the term given to leakage of air through the
connective tissue between the alveoli. Collateral ventilation may
include leakage of air through pathways that include the
interalveolar pores of Kohn, bronchiole-alveolar communications of
Lambert, and interbronchiolar pathways of Martin.
[0129] Drug delivery using a nebulizer may have benefits over a
single pulse delivery of drugs. Using a nebulizer allows for
multiple breaths which may allow the therapeutic agent to
effectively reach further into the parenchymal tissue allowing for
better distribution and absorption. Incorporating a one-way valve
or constant positive pressure through the delivery conduit of the
conduit may also be used to ensure that the drug is moving into the
lung. However, it is unnecessary for the nebulizer to provide gas
at positive pressure to introduce the aerosol, mist or powder into
the lung through the pneumostoma. The nebulizer may provide an
aerosol, mist or powder suspended in air/gas at or near ambient
pressure. Reduced pressure in the pneumostoma during inhalation by
the patient creates a sufficient pressure differential to suck the
aerosol, mist or powder suspended in air/gas into the pneumostoma.
A one way valve is configured to prevent air (and therapeutic
agent) from being exhaled out of the pneumostoma when the patient
exhales. Alternatively, the nebulizer may provide a slight positive
pressure using a fan, pump or the like.
[0130] The use of nebulizer 600, as shown in FIG. 6, avoids common
disadvantages of inhaled nebulizers. When using inhaled nebulized
therapeutic agents, the patient must wear a mask thus making
communication difficult. Also, the inhaled agents often taste
unpleasant and may cause undesirable side effects in tissues
outside the lung, such as the mouth. Drug delivery device 610 of
FIG. 6 delivers the therapeutic agent directly to the lung tissue
via pneumostoma 110 thereby increasing efficiency of the delivery
and reducing discomfort to the patient. The drug delivery device
610 may also be advantageously utilized to deliver low pressure
therapeutic gases to the patient, for example, oxygen.
[0131] FIGS. 7A and 7B show views of an alternative drug delivery
device 710 according to an embodiment of the present invention.
FIG. 7A shows a perspective view of an alternative drug delivery
device 710. FIG. 7B shows a sectional view of the drug delivery
device 710. As shown in FIG. 7A, drug delivery device 710 includes
a therapeutic agent dispenser 716 attached to a conical flange 714.
Conical flange 714 is formed of a compliant material such that it
can form a seal when pushed against a PMD. The conical shape is
designed to center drug delivery device 710 over a PMD to
facilitate engagement of the PMD by the drug delivery device 710.
Conical flange 714 may be provided with surface features to enhance
the formation of a temporary seal between flange 714 and the PMD. A
joint 718 is shown between therapeutic agent dispenser 716 and
conical flange 714 because it is preferred that a stiffer material
be used for therapeutic agent dispenser 716 and a more flexible
material be used for conical flange 714 which mates with the PMD.
The parts may be formed separately and then joined by welding,
gluing or otherwise bonding/connecting. Note that, for safety
reasons, each of the components of drug delivery device 710 is
preferably too large to fit through the tube 742 of a PMD. This
prevents aspiration of any of the components into the lung even in
the event of damage to drug delivery device 710.
[0132] As shown in FIG. 7B, drug delivery device 710 includes a
pressurized canister 768 is received in a sleeve 770. The outlet
valve 769 of pressurized canister 768 engages a fixture 772 in the
bottom of sleeve 770. When the user pushes canister 768 down into
sleeve 770, fixture 772 activates valve 769 to release a metered
dose of therapeutic agent in a propellant gas. The therapeutic
agent and gas passes through a channel 774 in fixture 772 and are
ejected into and through tube conical flange 714 as shown by arrow
776. The alternative drug delivery mechanisms previously discussed
may also be used with a drug delivery device having a PMD interface
shown in FIG. 7B.
[0133] As shown in FIG. 7B, the drug delivery device 710 operates
in conjunction with a pneumostoma management device (PMD) 740
located within a pneumostoma 110. In the PMD 740 of FIG. 7B, tube
742 is formed in one piece with (or permanently attached to) a
flange 744. PMD 740 has a hydrophobic filter 746 press fit into the
proximal end of tube 742 which may be removed to allow use of drug
delivery device 710 (as shown in FIG. 7B). Drug delivery device 710
may however be used or modified to be used with a PMD having a
different design than shown in FIG. 7B.
[0134] As shown in FIG. 7B, conical flange 714 provides a mating
section designed to mate and make a temporary seal with PMD 740. As
shown in FIG. 7B, to use drug delivery device 710, hydrophobic
filter 746 is first removed from PMD 740. Conical flange 714 is
then pushed into contact with the opening of tube 742. The tip of
conical flange 714 fits in the space left by the removal of
hydrophobic filter 746. Conical flange 714 centers drug delivery
device 710 as it is pushed into tube 742. Conical flange 714 also
deforms slightly to make a seal against PMD 740. When conical
flange 714 has formed a temporary seal with PMD 740, therapeutic
agent dispenser 716 is operated to dispense the therapeutic agent
through the tube 742 of PMD 740 into the pneumostoma 110. The
patient holds drug delivery device 710 against PMD 740 during
dispensing the therapeutic agent and for some seconds thereafter
(preferably 3-30 seconds). After dispensing the therapeutic agent,
the drug delivery device 710 is removed and the hydrophobic filter
746 is press fit into the proximal end of the tube 742.
Alternatively PMD 740 may be replaced with a new PMD 740.
[0135] Referring now to FIGS. 8A and 8B which show views of an
alternate drug delivery device 860 designed to be used in
conjunction with PMD 801 of FIGS. 8A and 8B as part of a
pneumostoma management system. FIG. 8A shows a perspective view of
drug delivery device 860. FIG. 8B shows a sectional view through
drug delivery device 860 of FIG. 8A when engaged with a chest mount
802. As shown in FIGS. 8A and 8B, drug delivery device 860 includes
a therapeutic agent dispenser 862 and a coupling 864. Drug delivery
device 860 is configured such that coupling 864 may be easily
engaged with aperture 224 of a chest mount 202. Coupling 864 is
designed such that it is too large to pass through aperture 224 of
chest mount 202 thereby preventing insertion of drug delivery
device 260 into pneumostoma 110. Coupling 864 may optionally be
provided with a feature such as a lip 865 for releasably engaging
lip 227 of recess 228 of chest mount 202.
[0136] As shown in FIGS. 8A and 8B, coupling 864 is cone-shaped
being somewhat narrower at the distal end for ease of insertion
into the chest mount 202. The coupling has an aperture 866 in the
distal end (shown by dashed line). The conical coupling facilitates
the engagement of the chest mount 202 by the drug delivery device
860. It is advantageous to simplify this engagement in order to
allow the patients to more readily comply with their drug delivery
protocols. The conical coupling also self centers over the
pneumostoma 110. Even if the coupling 864 is off center when it
first contacts chest mount 202, the conical shape pushes coupling
864 towards center as it enter chest mount 202.
[0137] It is also preferable for coupling 860 to make a good seal
with the chest mount 202 so that leakage of propellant gas and
therapeutic agents is reduced and delivery to the pneumostoma is
increased. For this reason, the coupling 864 is preferably made of
a relatively soft and compliant material that makes a good seal
with chest mount 202 when pushed up against chest mount 202 with a
modicum of force. The outer surface of coupling 864 may also be
provided with structural features to promote such sealing e.g.
ridge 865. In combination, the features of coupling 864 serve to
increase delivery of the therapeutic agent to the pneumostoma.
[0138] Therapeutic agent dispenser 862 includes a mechanism for
providing an aerosol, mist or powder in suspended in a propellant
gas under sufficient positive pressure to enter the lung through
the tube. The therapeutic agent dispenser preferably provides
positive pressure to push the therapeutic agent into the
pneumostoma. Suitable therapeutic agent dispenser mechanisms for
providing metered doses of therapeutic agents in a propellant gas
are known. Suitable therapeutic agent dispensers include
therapeutic agent dispensing mechanisms found in nebulizers,
ultrasonic nebulizers, metered dose inhalers and dry powder
inhalers. Dry powder therapeutic agent dispensers deliver a fine
microcrystalline suspension of therapeutic agent.
[0139] Referring again to FIGS. 8A and 8B therapeutic agent
dispenser 862 includes a pressurized canister 868 received in a
sleeve 870. The outlet valve 869 of canister 868 engages a fixture
872 in the bottom of sleeve 870. When the user pushes canister 868
down into sleeve 870, fixture 872 activates valve 869 to release a
metered dose of therapeutic agent in a propellant gas. The
therapeutic agent and propellant gas pass through a channel 874 in
fixture 870 and are ejected into through aperture 866 of coupling
864, through aperture 224 of chest mount 202 and into pneumostoma
110 as shown by arrow 876.
[0140] Note that in some embodiments it is unnecessary for
therapeutic agent dispenser 862 to provide a propellant gas at
positive pressure to introduce the aerosol, mist or powder into the
lung through the pneumostoma. In some embodiments the therapeutic
agent dispenser 862 provides the therapeutic agent/gas mixture at
or near ambient pressure. Reduced pressure in the pneumostoma
during inhalation by the patient creates a pressure differential
which sucks the therapeutic agent suspended in air/gas into the
pneumostoma.
[0141] Chest mount 202 is first positioned over a pneumostoma and
secured with adhesive to the skin of the patient. In a preferred
embodiment, the chest mount 202 remains attached for up to a week
thereby avoiding irritation of the skin caused by daily attachment
and removal of a mount. Chest mount may be positioned by the
patient by manual alignment of the aperture 224 of chest mount 202
with the aperture of the pneumostoma 112. Alternatively a
pneumostoma vent or an alignment tool may be used to align the
chest mount.
[0142] To use drug delivery device 860 in combination with chest
mount 202 Drug delivery device 860 is then inserted through the
aperture in the chest mount until coupling 864 engages the chest
mount 202. Drug delivery device 860 is pushed up against chest
mount 202 so that coupling 864 centers aperture 866 over aperture
224 of the chest mount and pneumostoma 112. Pushing drug delivery
device 860 against chest mount 202 also serve to make a temporary
seal between coupling 864 and chest mount 202. The temporary seal
reduces leakage of therapeutic agent. Drug delivery device 860 is
then operated to supply the aerosolized or dry powder therapeutic
agent directly to the parenchymal tissue of the lung through
pneumostoma 112 by operation of therapeutic agent dispenser 862.
The drug delivery device 860 may be operated either by the patient,
caregiver or medical practitioner.
[0143] FIG. 8C shows an example of a method of using a drug
delivery device according to embodiments of the present invention.
The method may be described in instructions for use provided to the
patient with the drug delivery device. At step 880, the patient
adjusts the pneumostoma management device. Depending on the
operation of the drug delivery device, this step may involve, for
example, removing a component of the pneumostoma vent such as the
filter; or removing the pneumostoma vent. At step 882, the patient
loads a dose of the therapeutic agent into the drug delivery
device. In some cases, the therapeutic agent is provided in single
dose containers and thus this will involve loading a single dose
package or indexing a package containing multiple singe dose
containers to a full container. In other cases, the therapeutic
agent will be in a multiple-use container, such as a pressurized
metered dose canister and it will be unnecessary for the patient to
load a therapeutic agent dose unless the container is empty. The
drug delivery device is now prepared for operation.
[0144] At step 884, the patient positions the distal end of the
coupling in the aperture of the chest mount or pneumostoma vent and
pushes the drug delivery device against the chest mount or
pneumostoma vent (which serves to accurately position aperture 866
of the drug delivery device and make a temporary seal between
coupling 864 and chest mount 202). As the distal end of the
coupling enters the aperture it centers the coupling. As the distal
tip is pushed against the aperture, the compliant surface makes a
temporary seal against the pneumostoma vent and/or chest mount.
After the coupling has centered and self-sealed, the therapeutic
agent may be administered.
[0145] In a typical therapeutic agent delivery operation the
patient will first exhale through the nose/mouth at step 885
immediately prior to actuating the drug delivery device. At step
886 the drug delivery device is actuated to mix the therapeutic
agents (aerosol, gas or dry powder) in the propellant/air. In some
embodiments this mixing step requires a relatively high air
speed/pressure. It may be undesirable for this airspeed/pressure to
be applied to the pneumostoma and thus the location of mixing step
886 may be separated by features to reduce the airspeed/pressure
distance before the mixture reaches the pneumostoma. Such features
may include, for example, space, volume, baffles and the like. At
step 888 application of positive pressure is used to propel the
mixture of therapeutic agent and propellant into the pneumostoma
and/or through the pneumostoma into the lung. The positive pressure
applied at this step may be substantially less than the pressure
used at step 886. The positive pressure may be supplied by a
different mechanism or by a modulation of the same mechanism. Steps
886 and 888 may be combined in one step for example where the
pressure is modulated by the mechanics of the device such that a
higher local pressure is available in one part of the device to mix
the agent but is reduced by the time it reaches the pneumostoma.
Note that in some embodiments it is unnecessary for the therapeutic
agent dispenser to provide propellant gas at positive pressure to
introduce the aerosol, mist or powder into the lung through the
pneumostoma. In some embodiments the drug delivery device remains
at or near ambient pressure and reduced pressure in the pneumostoma
during inhalation by the patient creates a pressure differential
which sucks the aerosol, mist or powder suspended in air/gas into
the pneumostoma.
[0146] At step 890, air is introduced through the pneumostoma to
aid distribution of the therapeutic agent through the lung tissue
by collateral ventilation. Step 890 is optional and may in some
cases be combined with step 888. In some cases step 890 may be
achieved by the patient "inhaling" through the pneumostoma in which
the patient expands the ribcage thereby creating a negative
pressure in the chest to draw air in through the pneumostoma. In
some circumstances this "inhalation" through the pneumostoma may be
enhanced by obstructing the nose and mouth while expanding the
ribcage. However, step 890 may not be necessary and a therapeutic
agent may be efficiently distributed from the pneumostoma through
parenchymal tissue of the lung by collateral ventilation without
the need for additional intake of air through the pneumostoma.
[0147] At step 892, the patient optionally holds their breath for a
time prior to exhaling, such as 10 to 15 seconds. This step may not
be necessary for therapeutic agents delivered into the pneumostoma.
Because the therapeutic agent was not delivered through the natural
airways, it will not be rapidly exhaled through the natural
airways. Indeed, in some cases breathing normally (while
obstructing the pneumostoma) while cause rapid distribution of the
therapeutic agent through the lung with little loss of therapeutic
agent due to exhalation. In some case it may be advantageous to
provide a slight positive pressure of air to the pneumostoma after
delivery of the therapeutic agent to promote diffusion of the
therapeutic agent through the lung. Steps 884 and 892 may be
repeated a number of times if necessary to deliver multiple doses
of therapeutic agent as shown by dashed arrow 894.
[0148] It may be desirable to leave the drug delivery device in
place for a period after delivery of therapeutic agent to prevent
the agent from being ejected through the pneumostoma. After the
therapeutic agent has been delivered, the drug delivery device is
pulled away from the chest mount and/or pneumostoma vent at step
896. At step 898, any removed components of the pneumostoma
management device are reattached. Any or all of the above steps may
be performed and/or controlled by a physician or caregiver instead
of the patient. The therapeutic agent delivery steps may be
repeated according to a particular dosing schedule or as needed
depending on the therapeutic agent and/or physician's
instructions.
[0149] FIGS. 9A and 9B show an alternative drug delivery device 910
to supply a therapeutic agent in/through a pneumostoma. The drug
delivery device 910 operates in conjunction with a pneumostoma
management device (PMD) 940 located within a pneumostoma 110. In
the PMD 940 of FIGS. 9A and 9B, tube 942 is formed in one piece
with (or permanently attached to) a flange 944. PMD 940 has a
hydrophobic filter 946 press fit into the proximal end of tube 942
and has a biocompatible adhesive 948 on the contact surface 949 of
flange 944 for releasably securing flange 944 to the skin 114 of
the patient's chest 100. As shown in FIG. 9D, drug delivery device
910 has a mating section 912, having a mating surface 914 designed
to mate and make a temporary seal with the exterior surface of
flange 944. Mating section 912 also has a distal tip 916 designed
to aid in the coupling of mating section 912 with PMD 940.
[0150] Drug delivery device 940 is utilized with PMD 940 while the
tube 942 of PMD 940 is within pneumostoma 110. As shown in FIG. 9A,
to use drug delivery device 910, hydrophobic filter 946 is first
removed by pulling on tab 950. Distal tip 916 of mating section 912
is placed against PMD 940. Distal tip 916 guides mating section 912
into the aperture of PMD 940. As drug delivery device 910 is pushed
towards PMD 940, distal tip 916 centers mating section 912 over the
aperture in the PMD 940 aligning aperture 918 with the PMD 940.
Mating surface 914 of mating section 912 contacts flange 944.
Mating section 914 is made of a compliant material and thus forms a
temporary seal between the drug deliver device 910 and the PMD 940.
In this embodiment, mating section 912 fits in the space left by
the removal of hydrophobic filter 946 as shown in FIG. 9B. When
mating section 912 has formed a temporary seal with flange 944,
therapeutic agent dispenser 916 is operated to dispense the
therapeutic agent through the tube 942 of PMD 940 into the
pneumostoma 110. After dispensing the therapeutic agent, the drug
delivery device 910 is removed and the hydrophobic filter 946 is
press fit into the proximal end of the tube 942. Alternatively PMD
940 may be replaced with a new PMD 940.
Pneumostoma Assessment Using Gas
[0151] Measurement of gases entering or leaving the pneumostoma may
be useful for assessing the functionality of the pneumostoma. The
ability of gas to pass through the pneumostoma may be measured in a
number of ways. First, gas flow through the pneumostoma can be
measured passively by placing a device over the pneumostoma which
measures airflow out of and/or into the pneumostoma during regular
breathing of the patient. Essentially, gases exiting the
pneumostoma are collected by a system which records the volume of
gas. Additionally, the gas may be analyzed to determine composition
of the gases exiting the pneumostoma.
[0152] As shown in FIG. 10A, a gas analysis device 1000 is inserted
into the pneumostoma 110 of a patient. Gas analysis device 1000 is
connected by tube 1002 to gas analyzer 1012. The gases exhaled from
the pneumostoma 110 may then be examined during normal breathing or
during an exercise test. The exhaled gas may be examined to
determine oxygen and carbon dioxide concentrations. In some cases,
the concentrations are compared to oxygen and carbon dioxide
concentrations in the gases exhaled through the natural airways.
Such evaluation may be useful in determining the effectiveness of a
pneumostoma and the location and/or desirability of additional
pneumostomas. The output of gas analyzer 1012 may be provided to a
computer system 1014 to display the results of the gas analysis.
Optionally, a mask 1016 may be provided. Mask 1016 may be used to
measure the volume of gas inhaled and exhaled by the patient
through the natural airways. The volume of gas inhaled and exhaled
through the natural airways may be compared to the volume of gas
exiting the pneumostoma.
[0153] In another example, a diagnostic gas is introduced through
the natural airways and the expiration of gases from the
pneumostoma is measured. As shown in FIG. 10A, optional mask 1016
may be used to provide a diagnostic gas mixture 1018 via the
natural airways. The concentration of gases exiting the pneumostoma
110 may be compared to the concentration of gases in the diagnostic
gas supply 1018. The time-course of exhalation of diagnostic gases
through the pneumostoma may be analyzed by gas analyzer 1012 to
evaluate the function of the pneumostoma and the prevalence of
collateral ventilation pathways connecting the pneumostoma to the
remainder of the lung. Such evaluation may be useful in determining
the effectiveness of a pneumostoma and the location and/or
desirability of additional pneumostomas. Gas analysis equipment may
be connected to a PMD and/or pneumostoma using one of the several
techniques and mechanisms described herein.
[0154] Alternatively, gas may be provided through the pneumostoma
from outside the chest of the patient. The gas is preferably
supplied at a controlled pressure slightly above the ambient air
pressure so as not to cause injury to the pneumostoma. In a simple
case, the rate of flow of gas into the lung through the pneumostoma
may be measured. The rate of gas flow may be used to assess the
patency of the pneumostoma. Alternatively, diagnostic gases may be
introduced through the pneumostoma for assessing collateral
ventilation and gas exchange. Diagnostic gases may be helpful in
measuring functional attributes of the pneumostoma and the lung. In
particular, introduction of diagnostic gases through the
pneumostoma may be useful for assessing gas diffusion between the
pneumostoma and the lung.
[0155] In one example, a diagnostic gas is introduced through the
pneumostoma and the gas is measured as it is exhaled through the
natural airways. The diagnostic gas may, for example, be a gas
mixture such as DLCO gas used in diffusion spirometry (which
nominally consists of 10% helium, 3000 ppm carbon monoxide and the
balance air). Gases exhaled through the natural airways are
analyzed to determine gas concentrations. The time course of
exhalation of the diagnostic gas is indicative of factors such as
pneumostoma functionality and collateral ventilation. Where the
diagnostic gas is introduced via the pneumostoma the time course of
exhalation of gas through the natural airways may be analyzed to
evaluate the function of the pneumostoma and the prevalence of
collateral ventilation pathways connecting the pneumostoma to the
remainder of the lung. Such evaluation may be useful in determining
the effectiveness of a pneumostoma and the location and/or
desirability of additional pneumostomas. A supply of the diagnostic
gas may be connected to a PMD and/or pneumostoma using one of the
several techniques and mechanisms described herein.
[0156] FIG. 10B shows a schematic view of a lung assessment system
using introduction of diagnostic gas 1018 through a pneumostoma
110. As shown in FIG. 10B a gas analysis device 1000 is inserted
into the pneumostoma 110 of a patient. Gas analysis device 1000 is
connected by tube 1002 to a pressure regulated source of diagnostic
gas 1018. A solenoid-controlled valve 1006 in tube 1002 controls
the flow of diagnostic gas into pneumostoma 110. The patient is
provided with a mask 1016 which allows the patient to inhale
ambient air but that collects the exhaled air and passes it to gas
analyzer 1012. During exhalation, a portion of the exhaled gases is
collected in a sample collection system and then analyzed using
discrete gas sensors and/or a gas chromatograph. The gas analyzer
1012 and the solenoid-controlled valve 1006 are connected to a
control system 1020 which may be a general purpose computer.
Control system 1020 controls solenoid-controlled valve 1006 and
receives data from gas analyzer 1012. Control system 1020 analyzes
the gas concentrations in the gas exhaled by the patient and
factors the relative values with inspired gas volume and other
parameters to calculate factors related to collateral ventilation
and pneumostoma function.
[0157] Introduction of diagnostic gases through a pneumostoma may
also be used to enhance imaging the lung with a CT scan or NMR
scan. For example polarized Helium-3 may be utilized to enhance
nuclear magnetic resonance/magnetic resonance imaging of the lung
(analogous to the way contrast agents enhance X-ray imaging). For
example, polarized helium-3 may be produced with lasers and the
magnetized pressurized gas may be stored for several days. When
introduced into the lung, the polarized helium-3 can be imaged with
an MRI-like scanner which produces breath-by-breath images of lung
ventilation, in real-time. Polarized helium-3 may thus, be used to
visualize airways in static or dynamic fashion. Alternative gases
which may be used as visualization agents include gaseous
radionuclide xenon or technetium DTPA in an aerosol form.
[0158] Introducing a controlled amount of a visualizable gas, e.g.
polarized Helium-3, through the pneumostoma and imaging the
diffusion of the gas into the lung over time may be utilized for
quantitative evaluation of the function of the pneumostoma and the
prevalence of collateral ventilation pathways connecting the
pneumostoma to the parenchymal tissue of the lung. Measuring the
time-course variations in diffusion of Helium-3 into the lung
allows analysis of diffusion coefficients for areas of the lung.
Such evaluation may be useful in determining the effectiveness of a
pneumostoma and the location and/or desirability of additional
pneumostomas. A source of polarized Helium-3 may be connected to a
PMD and/or pneumostoma using one of the several techniques and
mechanisms described herein.
[0159] FIG. 10C shows a schematic view of a lung assessment system
using a diagnostic gas in conjunction with an imaging scanner 1050.
Scanner 1050 may be an MRI, NMR, CT or X-Ray so long as the
particular diagnostic gas used may be successfully imaged with the
system. As shown in FIG. 10B, gas analysis device 1000 is inserted
into the pneumostoma 110 of a patient. Gas analysis device 1000 is
connected by tube 1030 to a pressure-regulated source of a
visualizable gas (e.g. polarized Helium-3). A solenoid-controlled
valve 1032 in tube 1030 controls the flow of diagnostic gas into
pneumostoma 110. The scanner 1050 and the solenoid-controlled valve
1032 are connected to a control system 1020 (not shown) which may
be a general purpose computer. The control system 1020 (not shown)
controls solenoid-controlled valve 1032 and receives data from
scanner 1050. The control system 1020 coordinates the introduction
of diagnostic gas into the patient with the patient's breathing and
also with the operations of scanner 1050 in order to accurately
image dispersion of the diagnostic gas from the pneumostoma 110 to
other parts of the lung. Control system 1020 analyzes the time
course distribution of the diagnostic gas from the pneumostoma into
the lung tissues to calculate factors related to collateral
ventilation and pneumostoma function, e.g. diffusion
coefficients.
[0160] FIGS. 10D and 10E show views of the gas analysis device 1000
of FIGS. 10A-10C. FIG. 10D shows a perspective view of the gas
analysis device 1000 while FIG. 10E shows a sectional view of gas
analysis device 1000 positioned within a pneumostoma. In general
terms, gas analysis device 1000 is a device which can be secured
into a pneumostoma for sampling gases exiting the pneumostoma
and/or providing gases into the pneumostoma. Gas analysis device
1000 can form part of a system which utilizes such gas sampling or
gas provision for assessment of pneumostoma function and/or lung
function. As used in FIGS. 10A and 10C, gas analysis device 1000 is
used to introduce diagnostic gas into the pneumostoma. As used in
FIG. 10B, gas analysis device 1000 is used to collect gases exhaled
from the lung for analysis by gas analyzer 1012.
[0161] Referring to FIG. 10D, gas analysis device 1000 includes a
hollow tube 1060 for insertion into the pneumostoma. Hollow tube
1060 is surrounded by a flange 1062 which secures tube 1060 in
position in the pneumostoma. Hollow tube 1060 connects to a
coupling 1064 on the proximal side of flange 1062. Coupling 1064 is
configured so that tube 1002 may be readily connected and
disconnected. Hollow tube 1060 has one or more holes 1066 at the
distal end through which gas may pass into or out of the
pneumostoma. Hollow tube 1060 and flange 1062 also provide a
temporary seal which inhibits leakage of gas from around hollow
tube 1060.
[0162] FIG. 10E shows a sectional view of gas analysis device 1000
of FIGS. 10A-4D in position in a pneumostoma 110. It is preferable
to minimize leakage of gases into or out of the pneumostoma. Flange
1062 is thus provided with an adhesive coating 1068 on the distal
surface to provide a temporary seal between the gas analysis device
1000 and the skin of the chest of the patient. Surface features may
also be provided on the distal surface of flange 1062 or on tube
1060 to promote sealing between gas analysis device 1000 and the
pneumostoma. For example, a circular ridge 1070 is shown in section
on FIG. 10E. Gas analysis device 1000 is preferably a disposable
component that will be used only with one patient. One or more
filters may be interposed between gas analysis device 1000 and the
gas supply and/or gas analyzer to prevent possible
cross-contamination between patients.
Delivery of Therapeutic Agents By the PMD/Vent
[0163] The tube of a PMD such as pneumostoma vent system 1100 may
be designed to deliver a pharmaceutically-active substance. A
"pharmaceutically-active substance" is an active ingredient of
vegetable, animal or synthetic origin which is used in a suitable
dosage as a therapeutic agent for influencing conditions or
functions of the body, as a replacement for active ingredients
naturally produced by the human or animal body and to eliminate or
neutralize disease pathogens or exogenous substances. The release
of the substance in the environment of pneumostoma vent has an
effect on the course of healing and/or counteracts pathological
changes in the tissue due to the presence of pneumostoma vent. In
particular, it is desirable in some embodiments to coat or
impregnate pneumostoma vent with pharmaceutically-active substances
that preserve the patency of pneumostoma and/or are antimicrobial
in nature but that do not unduly irritate the tissues of the
pneumostoma. In particular cases, suitable pharmaceutically-active
substances may have an anti-inflammatory and/or antiproliferative
and/or spasmolytic and/or endothelium-forming effect, so that the
functionality of the pneumostoma is maintained. However the
pneumostoma vent may also deliver, be coated with or be impregnated
with time-release therapeutic agents design to have effects on
tissues other than the tissues of the pneumostoma. Suitable
pharmaceutically-active substances include those described
above.
[0164] FIGS. 11A-11C shows different views of a pneumostoma vent
system 1100 (a pneumostoma management device). Pneumostoma vent
system 1100 is designed for use without a chest mount although it
could be adapted for use with a chest mount. FIG. 11A shows an
exploded view of the four main components of pneumostoma vent
system. From right to left these components are annular adhesive
cover 1102, filter 1104, pneumostoma vent 1106 and hydrocolloid
ring 1108.
[0165] Annular adhesive cover 1102 is a thin porous biocompatible
membrane which is adhesive on the surface facing the pneumostoma
(the inner surface see 1122 in FIG. 11C) and non-adhesive on the
outer surface 1120. A suitable material for annular adhesive cover
1102 is a CHG Chlorhexidine Gluconate IV Securement Dressing
available under the Tradename TEGADERM.TM. from 3M of St. Paul,
Minn. TEGADERM.TM. is thin layer of polyurethane bonded to a thin
hydrocolloid adhesive layer. The film is biocompatible as well as
thin, strong, and breathable. Other thin biocompatible dressings
and adhesive films may be used as an alternative to TEGADERM.TM..
Annular cover 1102 has an aperture 1124 large enough to allow air
to exit through filter 1104. Aperture 1124 may however be slightly
smaller than filter 1104 so that annular cover can be used to
secure filter 1104 to pneumostoma vent 1106. Exposed portions of
annular adhesive cover 1102 are provided with a paper cover to
protect the adhesive ring prior to use.
[0166] Filter 1104 is a circular disc of filter material. Filter
1104 is preferably a hydrophobic filter material, for example
GORETEX. Filter 1104 is larger than the proximal aperture in
pneumostoma vent 1106 and is positioned over the proximal aperture
to filter material moving in and out of the pneumostoma vent 1106.
Filter 1104 may be secured to pneumostoma vent 1106 by and
adhesive, welding, or other bonding technology. Filter 1104 may
also be secured to pneumostoma vent 1106 by annular adhesive cover
1102 instead of or in addition to other bonding techniques.
[0167] Pneumostoma vent 1106 comprises a tube 1130 for entering the
pneumostoma. As previously discussed, tube 1130 has an atraumatic
tip 1165 and one or more apertures 1167 in the distal end to allows
gases and discharge to enter tube 1130 from the pneumostoma. Tube
1130 is connected to a flange 1132 at the proximal end. Flange 1132
may be formed in one piece with tube 1130 or formed separately and
joined to tube 1132 as previously described with respect to other
embodiments. The proximal opening 1163 of pneumostoma vent is sized
so that filter 1104 covers proximal opening 1163. Filter 1104 is
secured over proximal opening 1163 as described in the previous
paragraph.
[0168] Hydrocolloid ring 1108 is a biocompatible hydrocolloid
material which is adhesive on both sides. Hydrocolloid ring may be
provided with a film coating and a transitional adhesive on the
side facing flange 1132 and annular cover 1102 in order to better
secure hydrocolloid ring 1108 to the flange and annular cover.
Hydrocolloid ring 1108 is preferably less than 3 mm thick and is
more preferably, approximately 1 mm in thickness. Exposed portions
of hydrocolloid ring 1108 are provided with a paper cover to
protect the adhesive ring prior to use.
[0169] Pneumostoma vent system 1100 may be provided as a kit of
separate components or one or more of the components may be
preassembled when provided to the patient. FIG. 11B shows an
assembly of all four main components including annular adhesive
cover 1102, filter 1104, pneumostoma vent 1106 and hydrocolloid
ring 1108. Note that tube 1130 fits through the middle of
hydrocolloid ring 1108. Note also that flange 1132 is trapped
between annular adhesive cover 1102 and hydrocolloid ring 1108. In
this embodiment, filter 1104 is also secured to pneumostoma vent
1106 by annular adhesive cover 1102. Exposed adhesive regions of
annular adhesive ring 1102 and hydrocolloid ring 1108 on the
patient side of the pneumostoma vent system assembly are provided
with protective covers (for example paper covers) to protect the
adhesive during shipping and prior to use. The completed or
partially completed assembly is provided as a sterile product to
the patient or caregiver who inserts the pneumostoma vent into a
pneumostoma as part of a pneumostoma care program.
[0170] FIG. 11C shows a sectional view of the pneumostoma vent
system 1100 in position within a pneumostoma 110. As shown in FIG.
11C, tube 1130 is inserted into the pneumostoma and passes through
the chest wall into the lung. Aperture 1167 in the distal end of
tube 1130 is positioned inside the lung so that gases and discharge
may enter the tube 1130 of the pneumostoma vent system. Flange 1132
of pneumostoma vent 1106 is secured to the skin of the patient by
hydrocolloid ring 1108 and annular adhesive cover 1102. Flange 1132
secures the position of tube 1130 within pneumostoma 110. Flange
1132 secures the position of aperture 1163 on the chest of the
patient such that gases from the lung may vent through tube 1130
and filter 1104. Both hydrocolloid ring 1108 and annular adhesive
cover 1102 contact the skin 114 of the patient to secure the
pneumostoma vent system. In some cases a barrier film may be
applied by the patient prior to securing the pneumostoma vent
system to reduce skin irritation caused by application and removal
of the system. An additional ring of absorbent material (not
shown), for example, gauze or another absorbent fabric may be
positioned around tube 1130 between hydrocolloid ring 1108 and the
skin 114 of the patient for absorbing any discharge from
pneumostoma 110 which escapes around tube 1130.
[0171] The components of the pneumostoma management system are
preferably supplied to the patient in sterile packaging. In
preferred embodiments, the components are supplied in packaging
that assists the patient in utilizing the components of the system
in the correct sequence. The packaging should include instructions
for use. The packaging may also be printed with material that
assists the patient in the appropriate sequence of the steps for
using the enclosed components. The package may also be designed to
provide the components to the patient in the order required for use
and maintain sterility during use. For example, the package may be
designed so that, upon opening the package, the components are
physically laid out in a tray in the order in which they are to be
used by the patient. Alternatively, the components may be provided
as individual components separately packaged. For example, cleaning
and moisturizing swabs and barrier spray/cream may alternatively or
additionally be packaged separately and provided to patient.
[0172] Referring again to FIG. 11C which shows a sectional view of
the pneumostoma vent system 1100 in position within a pneumostoma
110. As shown in FIG. 11C, tube 1130 is inserted into the
pneumostoma and passes through the chest wall into the lung. Tube
1130 may be coated with a pharmaceutically-active substance along
all or part of tube 1130.
[0173] As shown in FIG. 11C tube 1130 is provided with a
pharmaceutically-active coating 1140 including a
pharmaceutically-active substance. Coating 1140 is limited to the
distal tip of tube 1140. However coating may also be provided over
the entirety of tube 1130 or different coatings provided in
different regions of tube 1140 depending upon the intended function
of the coating. Coating 1140 is in contact with thin vascularized
epithelium of the pneumostoma at the perimeter of pneumostoma 110.
Thus depending on the pharmaceutical, the pharmaceutically-active
substance may diffuse from coating 1140 into the cells of the
pneumostoma, and from those cells into the bloodstream of the
patient. The coating 1140 preferably releases the
pharmaceutically-active substance over the time of use (such as a
day) to main dosage consistency. The pharmaceutically-active
substance may be selected to treat the tissues of the pneumostoma
for example to maintain patency, reduce tissue growth, or inhibit
infection. The pharmaceutically active substance may alternatively
be selected to treat the patient systemically for example by
providing a hormone to be absorbed into the blood stream via the
tissues of the pneumostoma.
[0174] As shown in FIG. 11C the material of tube 1130 of
pneumostoma vent system 1100 may also be impregnated with a
pharmaceutically-active substance 1142. Depending upon the
material, the pharmaceutically-active substance may be added before
or after forming the material into the desired shape. The
pharmaceutically-active substance is eluted from the tube 1130 over
time while the tube 1130 is in contact with the pneumostoma. The
tube 1130 preferably releases the pharmaceutically-active substance
gradually over the time of use (such as a day) to main dosage
consistency. The pharmaceutically-active substance may be selected
to treat the tissues of the pneumostoma for example to maintain
patency, reduce tissue growth, or inhibit infection. The
pharmaceutically-active substance may alternatively be selected to
treat the patient systemically for example by providing a hormone
to absorbed into the blood stream via the tissues of the
pneumostoma.
[0175] FIG. 11D shows an alternate embodiment of a pneumostoma vent
system 1150 with drug delivery features. As before, pneumostoma
vent system includes filter 1104, annular adhesive cover 1102,
hydrocolloid ring 1108. However vent 1156 comprises a tube 1160 for
entering the pneumostoma which has an additional lumen 1162 for
delivery of a pharmaceutically active substance fluid in addition
to the lumen 1161 through gases may escape from the pneumostoma.
Lumen 1161 passes along the length of tube 1130 and exits tube 1130
at one or more apertures 1164. One or more apertures 1164 are
preferably located in the distal half of tube 1160 so as to
releases the pharmaceutically active fluid into contact with highly
vascularized tissue in the lung to facilitate absorption. Vent 1156
has a flange 1158 at the proximal end. Lumen 1162 is accessible
through flange 1158 by means of access port 1166. Access port 1166
marks the location of lumen 1162. Access port 1166 is preferably
closed until mated with a device for supplying the pharmaceutically
active fluid into lumen 1162.
[0176] FIG. 11E shows an enlarged view of an embodiment of an
access port 1166. As shown in FIG. 11E access port 1166 is marked
by an opening 1170 in adhesive cover 1102 which exposes flange
1158. The distal end of lumen 1162 is obstructed by a diaphragm
1172. Diaphragm 1172 may be formed from cover 1102, the material of
flange 1158 or an additional thin piece of material. To access
lumen 1162 the sharp tip of a tube (not shown) pierces the
diaphragm allowing a fluid to be injected through the tube into the
lumen 1162. For example a syringe may be used with a short needle
to inject a pharmaceutically-active fluid through diaphragm into
lumen 1162. The fluid passes along lumen 1162 and out of aperture
1162 9 FIG. 11D) into the pneumostoma where it may be absorbed.
This is a suitable technique for periodic or intermittent supply of
a pharmaceutically-active fluid to the patient. Where a continuous,
regular and/or automatic supply of pharmaceutically-active fluid is
desired, a supply line 1180 may be coupled to lumen 1162 as shown
in FIG. 11E. Supply line 1180 is connected by a coupling 1182 to
access port 1166. Coupling 1182 may include an adhesive flange 1184
and a short needle 1186. Short hollow needle 1186 penetrates
diaphragm 1172 to connect supply line 1180 to lumen 1162. Access
port 1166 and coupling 1182 may include other suitable medical
connectors for connecting one tube to another, for example, Luer or
Tuohy Borst fittings. The other end (proximal end) of supply line
1180 is connected to a drug pump 1190. Drug pump 1190 (shown
schematically) is preferably a self-contained ambulatory unit
having a power supply 1192, pump 1194, pump controller 1196 and a
reservoir 1198 containing a supply of the pharmaceutically-active
fluid 1199. Drug pump 1190 may be, for example a belt mounted unit
approximately the size of a cell phone. Pump 1194 pumps a metered
supply of the pharmaceutically-active fluid 1199 from the reservoir
1198 into the supply line 1180 under the control of controller 1196
and powered by power supply 1192. Suitable portable drug pumps are
known in the art and described, for example, in U.S. Pat. No.
7,347,836 to Peterson et al. and references cited therein.
[0177] In use, controller 1196 meters the amount of
pharmaceutically-active fluid 1199 supplied to the patient
according to preset programming, user input or sensors. For
example, where the pharmaceutically-active fluid is insulin or an
insulin analog, controller 1196 may cause pump 1194 to supply
insulin to supply line 1180 in response to elevated glucose levels
detected by a glucose sensor. From supply line 1180 the
pharmaceutically-active fluid 1199 passes through coupling 1182 and
access port 1166 via lumen 1162 into the pneumostoma where it is
absorbed into the bloodstream of the patient. The present invention
has the advantage of providing a means for continuous
administration and rapid absorption of the pharmaceutically-active
fluid 1199 without requiring injection through the skin or oral
administration.
Materials
[0178] In preferred embodiments, the PMD and drug delivery device
are formed from biocompatible polymers or biocompatible metals. A
patient will typically wear PMD at all times and thus the
materials, particularly of tubes entering the pneumostoma, should
meet high standards for biocompatibility. In general preferred
materials for manufacturing the PMD and drug delivery device are
biocompatible thermoplastic elastomers that are readily utilized in
injection molding and extrusion processing. As will be appreciated,
other suitable similarly biocompatible thermoplastic or
thermoplastic polymer materials can be used without departing from
the scope of the invention. Biocompatible polymers for
manufacturing PMD and drug delivery device may be selected from the
group consisting of polyethylenes (HDPE), polyvinyl chloride,
polyacrylates (polyethyl acrylate and polymethyl acrylate,
polymethyl methacrylate, polymethyl-coethyl acrylate,
ethylene/ethyl acrylate), polycarbonate urethane (BIONATEG),
polysiloxanes (silicones), polytetrafluoroethylene (PTFE,
GORE-TEX.RTM., ethylene/chlorotrifluoroethylene copolymer,
aliphatic polyesters, ethylene/tetrafluoroethylene copolymer),
polyketones (polyaryletheretherketone, polyetheretherketone,
polyetherether-ketoneketone, polyetherketoneetherketoneketone
polyetherketone), polyether block amides (PEBAX, PEBA), polyamides
(polyamideimide, PA-11, PA-12, PA-46, PA-66), polyetherimide,
polyether sulfone, poly(iso)butylene, polyvinyl chloride, polyvinyl
fluoride, polyvinyl alcohol, polyurethane, polybutylene
terephthalate, polyphosphazenes, nylon, polypropylene,
polybutester, nylon and polyester, polymer foams (from carbonates,
styrene, for example) as well as the copolymers and blends of the
classes listed and/or the class of thermoplastics and elastomers in
general. Reference to appropriate polymers that can be used for
manufacturing PMD and drug delivery device can be found in the
following documents: PCT Publication WO 02/02158, entitled
"Bio-Compatible Polymeric Materials;" PCT Publication WO 02/00275,
entitled "Bio-Compatible Polymeric Materials;" and, PCT Publication
WO 02/00270, entitled "Bio-Compatible Polymeric Materials" all of
which are incorporated herein by reference. Other suitable
materials for the manufacture of the PMD include medical grade
inorganic materials such stainless steel, titanium, ceramics and
coated materials. Hydrophobic filter materials should be
sufficiently porous to allow air to exit through the filter.
Materials for hydrophobic filters are available commercially and
filters can be fabricated from any suitable hydrophobic polymer,
such as tetrafluoroethylene, PTFE, polyolefins, microglass,
polyethylene and polypropylene or a mixture thereof. In preferred
examples, the hydrophobic filter is a laminated tetrafluoroethylene
e.g. TEFLON.RTM., (E.I. du Pont de Nemours Co.) or GORE-TEX.RTM.
(W. L. Gore, Inc.) of a controlled pore size. In other examples the
hydrophobic filter may comprise a felted polypropylene;
PTFE/polypropylene filter media.
[0179] The foregoing description of preferred embodiments of the
present invention has been provided for the purposes of
illustration and description. It is not intended to be exhaustive
or to limit the invention to the precise forms disclosed. Many
embodiments were chosen and described in order to best explain the
principles of the invention and its practical application, thereby
enabling others skilled in the art to understand the invention for
various embodiments and with various modifications that are suited
to the particular use contemplated. Embodiments of the present
invention may use some or all of the features shown in the various
disclosed embodiments where such features are not structurally or
functionally incompatible. It is intended that the scope of the
invention be defined by the claims and their equivalents.
* * * * *