U.S. patent application number 10/360599 was filed with the patent office on 2003-10-02 for apparatus and method for dispersing dry powder medicaments.
This patent application is currently assigned to INHALE THERAPEUTIC SYSTEMS, a corporation of the State of California. Invention is credited to Anthony, Jack M., Axford, George S., Burr, John D., Etter, Jeffrey W., Smith, Adrian E..
Application Number | 20030183229 10/360599 |
Document ID | / |
Family ID | 26976958 |
Filed Date | 2003-10-02 |
United States Patent
Application |
20030183229 |
Kind Code |
A1 |
Smith, Adrian E. ; et
al. |
October 2, 2003 |
Apparatus and method for dispersing dry powder medicaments
Abstract
A method for aerosolizing a powdered medicament comprises
coupling a powder inlet end of a feed tube with a penetration in a
receptacle containing the powder. Powder is drawn upward through
the tube and dispersed in a high pressure gas stream flowing past a
portion of the feed tube. Apparatus comprise the feed tube mounted
within a base enclosure proximate a holder for one or more
receptacles, which may be in the form of a cartridge containing a
plurality of receptacles formed in a continuous web. The cartridge
may be reciprocated relative to the feed tube and a separate
piercing mechanism in order to sequentially piercing the receptacle
and thereafter couple the feed tube through the resulting
penetration for extracting the powder. Alternatively,
penetration(s) through the receptacle may be formed as the feed
tube is coupled, or some penetrations formed prior to coupling with
other penetrations formed at the time of coupling.
Inventors: |
Smith, Adrian E.; (Belmont,
CA) ; Burr, John D.; (Redwood City, CA) ;
Etter, Jeffrey W.; (Castro Valley, CA) ; Axford,
George S.; (Pacifica, CA) ; Anthony, Jack M.;
(Palo Alto, CA) |
Correspondence
Address: |
NEKTAR THERAPEUTICS
150 INDUSTRIAL ROAD
SAN CARLOS
CA
94070
US
|
Assignee: |
INHALE THERAPEUTIC SYSTEMS, a
corporation of the State of California
1001 East Meadow Circle
Palo Alto
CA
94303
|
Family ID: |
26976958 |
Appl. No.: |
10/360599 |
Filed: |
February 6, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10360599 |
Feb 6, 2003 |
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09583300 |
May 30, 2000 |
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6543448 |
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09583300 |
May 30, 2000 |
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09004558 |
Jan 8, 1998 |
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6089228 |
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09004558 |
Jan 8, 1998 |
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08487184 |
Jun 7, 1995 |
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5740794 |
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08487184 |
Jun 7, 1995 |
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08309691 |
Sep 21, 1994 |
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5785049 |
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Current U.S.
Class: |
128/203.12 ;
128/203.21 |
Current CPC
Class: |
A61M 15/0051 20140204;
A61M 15/0036 20140204; A61M 2202/064 20130101; A61M 2205/073
20130101; A61M 2205/0233 20130101; A61M 15/0045 20130101; A61M
15/0041 20140204; A61M 15/0055 20140204 |
Class at
Publication: |
128/203.12 ;
128/203.21 |
International
Class: |
A61M 015/00; A61M
016/10 |
Claims
What is claimed is:
1. An improved apparatus for aerosolizing a powdered medicament,
the apparatus being of the type having a housing and a source of
pressurized gas for aerosolizing the powder, wherein the
improvement comprises: a pressurization cylinder; a piston slidable
within the cylinder; a release valve in communication with the
cylinder; and a handle assembly having a handle operably attached
to the piston and a means for closing the valve, wherein
translation of the handle closes the valve and axially translates
the piston within the cylinder to produce the pressurized gas.
2. An improved apparatus as in claim 1, wherein the release valve
comprises a valve stem connected to a valve poppet, wherein the
means for closing the valve comprises a roller cam adjacent the
valve stem for translating the valve stem to close the valve as the
handle is translated radially outward from the housing.
3. An improved apparatus as in claim 2, wherein the handle assembly
further comprises a toggle link which moves over-center to hold the
roller cam against the valve stem and keep the valve closed.
4. An improved apparatus as in claim 3, wherein the handle assembly
further includes a linkage between the handle and the piston,
wherein the linkage reciprocally translates the piston between a
retracted position and a charged position within the cylinder as
the handle is translated radially outward and radially inward
relative to the housing.
5. An improved apparatus as in claim 4, further comprising an
interlocking means for preventing inward radial translation of the
handle until the toggle link has moved over-center.
6. An improved apparatus as in claim 5, wherein the interlocking
means comprises a ratchet and a pawl.
7. An improved apparatus as in claim 3, further comprising a
release button for translating the roller cam from the over-center
position to open the valve.
8. An improved apparatus as in claim 4, wherein the cylinder
includes a one-way valve for allowing air to enter the cylinder as
the piston is translated to the retracted position.
9. An improved apparatus as in claim 1, wherein the powdered
medicament is held within a receptacle, and further comprising a
feed tube having an inlet end, an outlet end, and a lumen extending
therebetween, wherein the inlet end may be inserted into the
receptacle so that compressed gas exiting the release valve may be
flowed past the outlet end, wherein powder from the receptacle is
extracted through the tube and dispersed in the flowing compressed
gas to form the aerosol.
10. An improved apparatus as in claim 9, further comprising means
for piercing at least one hole in an access surface of the
receptacle simultaneously with inserting the inlet end of the feed
tube into the receptacle.
11. An improved apparatus as in claim 10, wherein the piercing
means comprises a pair of pointed tabs, and wherein the tabs are
each disposed at an oblique angle relative to the access surface of
the receptacle when the tabs are pierced through the access
surface.
12. An improved apparatus as in claim 11, further comprising means
for reciprocally translating the receptacle toward and away from
the piercing means.
13. An improved apparatus as in claim 12, wherein the translating
means comprises an over-center linkage for locking the receptacle
in place upon insertion of the inlet end of the feed tube into the
receptacle.
14. An improved apparatus as in claim 13, further comprising a
positioning pin for aligning the receptacle in a preferred
orientation relative to the piercing means while inserting the
inlet end of the feed tube into the receptacle.
15. An improved apparatus as in claim 1, wherein the handle
assembly includes four linkages for attaching the handle to the
housing, wherein the handle may be translated radially outward and
radially inward relative to the housing with a generally constant
force.
16. An improved apparatus as in claim 1, further comprising means
on the housing for producing verbal operating instructions.
17. An apparatus for aerosolizing a powder held in a receptacle
having a puncturable access surface, the apparatus comprising: a
housing; a source of pressurized gas; a capture chamber attached to
the housing; and a transjector assembly held within the housing,
said transjector assembly having a means for piercing the access
surface of the receptacle and for receiving pressurized gas to draw
powder from the receptacle and into the capture chamber.
18. An apparatus as in claim 17, wherein the transjector assembly
receives gas directly from the gas source and delivers powder
directly to the capture chamber without powder passing through
other portions of the apparatus.
19. An apparatus as in claim 17, further comprising an interface
seal between the transjector assembly and the housing, whereby
pressurized gas may be passed from the housing to the transjector
assembly without substantial loss of the gas.
20. An apparatus as in claim 19, wherein the interface seal is
angled relative to a central axis of the transjector assembly.
21. An apparatus as in claim 17, further comprising a receptacle
seal for forming a seal between the transjector and the
receptacle.
22. An apparatus as in claim 17, wherein the transjector assembly
is keyed to be repeatedly received into the housing in a unique
orientation.
23. An apparatus as in claim 17, wherein the capture chamber is
axially slidable over the housing, whereby the capture chamber may
be placed in a collapsed position substantially covering the
housing or an extended position forming an enclosure for receiving
aerosolized powder.
24. An apparatus as in claim 23, further comprising at least one
detent pin in the housing and at least one notch in the capture
chamber, with the detent pin being received into the notch when the
capture chamber is in the extended position.
25. An apparatus as in claim 24, further comprising a spring for
outwardly biasing the detent pin.
26. An apparatus as in claim 24, wherein the detent pin and the
notch are generally V-shaped in geometry.
27. An apparatus as in claim 24, wherein the capture chamber
comprises an elongate chamber body having at least one elongate
ridge extending longitudinally along the body.
28. An apparatus as in claim 24, wherein the chamber body is
asymmetrical in cross-sectional geometry.
29. An apparatus as in claim 17, wherein the capture chamber
further includes a mouthpiece.
30. An apparatus as in claim 29, further comprising a cap removably
held over the mouthpiece.
31. An apparatus as in claim 30, further comprising a seal between
the cap and the mouthpiece.
32. A receptacle for holding a powdered medicament, the receptacle
being adapted to be received into an aperture in a housing of an
aerosolizing apparatus, the receptacle comprising: a receptacle
body having a puncturable access surface; and a tab extending from
the receptacle body, wherein the receptacle body may be received
into the aperture with at least a portion of the tab remaining
outside the housing.
33. A receptacle as in claim 32, wherein the tab includes a keyed
hole adapted to receive an alignment pin in the aerosolizing
apparatus.
34. An improved method for aerosolizing a powdered medicament, said
method being of the type wherein the powder is entrained and
suspended in a flowing gas stream, wherein the improvement
comprises: providing a housing having a pressurization cylinder, a
piston slidable within the cylinder, a release valve in
communication with the cylinder, and a handle for axially
translating the piston and for closing the release valve;
translating the handle away from the housing to axially translate
the piston within the cylinder to a retracted position and to close
the release valve; translating the handle back toward the housing
to translate the piston to a charged position and create a
pressurized gas; and releasing the valve to abruptly discharge the
pressurized gas.
35. An improved method as in claim 34, further comprising
preventing translation of the handle in the direction of the
housing until the release valve is closed.
36. An improved method as in claim 35, further comprising holding
the release valve closed while translating the handle back toward
the housing.
37. An improved method as in claim 34, wherein the handle is
translated away from and toward the housing with the handle being
generally parallel to the housing.
38. An improved method as in claim 34, further comprising supplying
a generally constant force when translating the handle toward the
housing when pressurizing the gas.
39. An improved method as in claim 34, further comprising
introducing the powder that is suspended in the released gas into a
capture chamber while simultaneously bleeding off a preselected
amount of gas from the capture chamber.
40. An improved method as in claim 34, further comprising providing
a transjector assembly for receiving the pressurized gas and
aerosolizing the powder, and periodically removing the transjector
assembly from the housing for cleaning.
41. An improved method as in claim 34, further comprising producing
verbal operating instructions from the housing.
42. An improved method as in claim 34, further comprising providing
a receptacle having a puncturable lid for holding the medicament
and translating the receptacle toward the transjector assembly
until the transjector assembly penetrates the lid.
43. An improved method as in claim 42, further comprising guiding
the receptacle toward the transjector so that the transjector
penetrates the lid at a known and a predictable position.
44. An improved method as in claim 42, further comprising holding
the receptacle with the transjector assembly penetrating the lid
until after the valve is released.
45. A method for aerosolizing a powdered medicament, said method
comprising: providing receptacles having a receptacle body and a
tab extending from the receptacle body, wherein the powdered
medicament is held within the receptacle bodies; inserting one
receptacle into a housing having an aperture, wherein the
receptacle body is received within the aperture and at least a
portion of the tab remains outside the housing; piercing the
receptacle body and extracting the powdered medicament in a gas
stream that can be inhaled; pulling on the tab to remove the
receptacle from the housing.
46. A method as in claim 45, wherein the housing has a
reciprocatable capture chamber for receiving the powder-bearing gas
stream, and further comprising deploying the chamber prior to
inserting the receptacle.
47. A method as in claim 46, wherein deploying the chamber exposes
the aperture and wherein the chamber cannot be retracted until the
receptacle is removed.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part application of
U.S. patent application Ser. No. 08/309,691, filed Sep. 21, 1994,
the disclosure of which is herein incorporated by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates generally to methods and
apparatus for the pulmonary delivery of drugs. More particularly,
the present invention relates to a method and apparatus for
dispersing dry powder medicaments for inhalation by a patient.
[0004] Effective delivery to a patient is a critical aspect of any
successful drug therapy. Various routes of delivery exist, and each
has its own advantages and disadvantages. Oral drug delivery of
pills, capsules, elixirs, and the like, is perhaps the most
convenient method, but many drugs are degraded in the digestive
tract before they can be absorbed. Such degradation is a particular
problem with modern protein drugs which are rapidly degraded by
proteolytic enzymes in the digestive tract. Subcutaneous injection
is frequently an effective route for systemic drug delivery,
including the delivery of proteins, but enjoys a low patient
acceptance. Since injection of drugs, such as insulin, one or more
times a day can frequently be a source of poor patient compliance,
a variety of alternative routes of administration have also been
developed, including transdermal, intranasal, intrarectal,
intravaginal, and pulmonary delivery.
[0005] Of particular interest to the present invention, pulmonary
drug delivery relies on inhalation of a drug dispersion or aerosol
by the patient so that active drug within the dispersion can reach
the distal (alveolar) regions of the lung. It has been found that
certain drugs are readily absorbed through the alveolar region
directly into blood circulation. Pulmonary delivery is particularly
promising for the delivery of proteins and polypeptides which are
difficult to deliver by other routes of administration. Such
pulmonary delivery is effective both for systemic delivery and for
localized delivery to treat diseases of the lungs.
[0006] Pulmonary drug delivery (including both systemic and local)
can itself be achieved by different approaches, including liquid
nebulizers, metered dose inhalers (MDI's) and dry powder dispersion
devices. Dry powder dispersion devices are particularly promising
for delivering protein and polypeptide drugs which may be readily
formulated as dry powders. Many otherwise labile proteins and
polypeptides may be stably stored as lyophilized or spray-dried
powders by themselves or in combination with suitable powder
carriers. The ability to deliver proteins and polypeptides as dry
powders, however, is problematic in certain respects. The dosage of
many protein and polypeptide drugs is often critical so it is
necessary that any dry powder delivery system be able to
accurately, and precisely (repeatedly) deliver the intended amount
of drug. Moreover, many proteins and polypeptides are quite
expensive, typically being many times more costly than conventional
drugs on a per-dose basis. Thus, the ability to efficiently deliver
the dry powders to the target region of the lung with a minimal
loss of drug is critical. It is further desirable that powder
agglomerates present in the dry powder be sufficiently broken up
prior to inhalation by the patient to assure effective systemic
absorption or other pulmonary delivery.
[0007] A particularly promising approach for the pulmonary delivery
of dry powder drugs utilizes a hand-held device with a pump or
other source of pressurized gas. A selected amount of the
pressurized gas is abruptly released through a powder dispersion
device, such as a Venturi tube, and the dispersed powder made
available for patient inhalation. While advantageous in many
respects, such hand-held devices are problematic in a number of
other respects. The particles being delivered are very fine,
usually being sized in the range from 1 .mu.m to 5 .mu.m, making
powder handling and dispersion difficult. The problems are
exacerbated by the relatively small volumes of pressurized gas,
typically 2 ml to 25 ml at 20 to 150 psig, which are available in
such devices. In particular, Venturi tube dispersion devices are
unsuitable for difficult-to-disperse powders when only small
volumes of pressurized gas are available. Moreover, Venturi tube
dispersion devices have very small powder inlet orifices which are
easily plugged by the powders used for pulmonary delivery. Another
requirement for hand-held and other powder delivery devices is high
dosage concentration. It is important that the concentration of
drug in the bolus of gas be relatively high to reduce the number of
breaths and/or volume of each breath required to achieve a total
dosage. The ability to achieve both adequate dispersion and small
dispersed volumes is a significant technical challenge.
[0008] It would therefore be desirable to provide methods and
systems for the dispersion of dry powder protein, polypeptide, and
other drugs which meet some or all of the above objectives.
[0009] 2. Description of the Background Art
[0010] Dry powder dispersion devices for medicaments are described
in a number of patent documents. U.S. Pat. No. 3,921,637 describes
a manual pump with needles for piercing through a single capsule of
powdered medicine. The use of multiple receptacle disks or strips
of medication is described in EP 467172 (where a reciprocatable
piercing mechanism is used to piercing mechanism through opposed
surfaces of a blister pack); WO91/02558; WO93/09832; WO94/08522;
U.S. Pat. Nos. 4,627,432; 4,811,731; 5,035,237; 5,048,514;
4,446,862; and 3,425,600. Other patents which show puncturing of
single medication capsules include U.S. Pat. Nos. 4,338,931;
3,991,761; 4,249,526; 4,069,819; 4,995,385; 4,889,114; and
4,884,565; and EP 469814. WO90/07351 describes a hand-held pump
device with a loose powder reservoir.
[0011] A dry powder sonic velocity disperser intended for
industrial uses and very high flow rates is described in Witham and
Gates, Dry Dispersion with Sonic Velocity Nozzles, presented at the
Workshop on Dissemination Techniques for Smoke and Obscurants,
Chemical Systems Laboratory, Aberdeen Proving Ground, Maryland,
Mar. 14-16, 1983.
[0012] A pneumatic powder ejector having a suction stage and an
injection stage is described in U.S. Pat. No. 4,807,814. The device
comprises an axial gas Venturi tube and a lateral powder inlet.
[0013] Pittman and Mason (1986), Solids Handling Conference, Paper
C4, pages C-41 to C-51, describes an ejector nozzle (FIG. 2) having
an annular air inlet upstream of a venturi restriction.
[0014] SU 628930 (Abstract) describes a hand-held powder disperser
having an axial air flow tube.
[0015] SU 1003926 (Abstract) describes a gas thermal coating
injector.
[0016] Bubrik and Zhelonkina (1978), "Ejector Feeders for Pneumatic
Transport Systems," in Chemical and Petroleum Engineering,
Consultants Bureau, New York, describes differing efficiencies in
several ejector designs.
[0017] Zholab and Koval (1979), Poroshkovaya Metallurgiya 6:13-16,
describes effects of injector design on particle size.
[0018] Bohnet (1984) "Calculation and Design of
Gas/Solid-Injectors," in Powder Technology, pages 302-313,
discusses conventional injector design.
[0019] Fox and Westawag (1988) Powder and Bulk Engineering, March
1988, pages 33-36, describes a venturi eductor having an axial air
inlet tube upstream of a venturi restriction.
[0020] NL 7712041 (Abstract) discloses an ejector pump which
creates suction and draws powder into a separator.
[0021] EP 347 779 describes a hand-held powder disperser having a
collapsible expansion chamber.
[0022] EP 490 797 describes a hand-held powder disperser having a
spring-loaded piston, where the piston carries a dispersion
nozzle.
[0023] U.S. Pat. No. 3,994,421, describes a hand-held powder
disperser having a collapsible deceleration chamber.
[0024] Pulmonary drug delivery is described in Byron and Patton
(1994) J. Aerosol Med. 7:49-75.
SUMMARY OF THE INVENTION
[0025] The present invention provides methods and apparatus for
efficient pulmonary delivery of accurate, precise, and repeatable
dosages of powdered medicaments. The present invention will be
particularly useful for the delivery of costly biopharmaceuticals
such as protein, polypeptide and polynucleic acid drugs, but will
also be useful for the systemic or localized delivery of any
powdered medicament through the lungs. The delivery system and
method produce substantially complete dispersion of the medicament
powder with the break-up of any agglomerates of the powder which
may have formed prior to delivery. The method and apparatus will
find particular use in the dispersion of finely powdered
medicaments from unit dosage receptacles, such as blister packs or
cartridges, where the present invention is able to fluidize and
extract substantially the entire amount of powder (usually at least
70% by weight, more usually at least 80%, and preferably at least
90%) within the receptacle, thus minimizing waste and enhancing the
accuracy and precision of the dosage. The methods and approaches,
however, will also find use with the dispersion and delivery of
preselected metered amounts (boluses) of powdered medicaments from
receptacles containing multiple dosage units, i.e. "bulk" powders
contained in a single receptacle.
[0026] The methods and apparatus of the present invention are
particularly suitable for the delivery of powders formed from
discrete particles in the size range from 1 .mu.m to 5 .mu.m. Such
powders, when properly dispersed in an aerosol, are optimum for
delivery into the alveolar regions of the lung. However, they are
particularly difficult to handle, and frequently become highly
agglomerated during processing, packaging, and handling.
Heretofore, handling characteristics of such powders have often
been enhanced by combining the fine drug particles with larger
carrier particles which have easier handling and dispersion
characteristics. Use of a carrier, however, dilutes the drug,
requiring a larger dispersion volume for a given drug dosage. The
carrier particles can also cause choking when inhaled and serve no
purpose other than improving handling characteristics. The present
invention is able to achieve dispersion of fine drug particles with
little or no carrier substances by a two-step dispersion method.
The present invention, however, will be functional with drug
compositions which include such carrier particles, as well as with
diluents which may be necessary to achieve desired dosage
concentrations.
[0027] The powders are first fluidized within the receptacle, as
described above, resulting in fluidized particles and particle
agglomerates which are then dispersed in the high velocity gas
stream under conditions which break up such agglomerates. Such
complete dispersion can be achieved with very low volumes of high
velocity air and fluidization air, resulting in a well dispersed
drug bolus having relatively high drug particle concentrations. Of
course, the present invention is useful as well with drug
formulations including a carrier diluent, or the like. The
advantage of the present invention is that the use of carriers can
often be reduced or eliminated altogether.
[0028] According to the method of the present invention, the
powdered medicament is contained in a receptacle having a
puncturable lid or other access surface. A powder inlet end of a
feed tube is coupled with, i.e. engaged against or inserted
through, a penetration in the access surface, and a high velocity
airstream (usually sonic which provides sufficient shear forces to
separate agglomerates into individual particles) is flowed past a
portion of the tube, such as an outlet end, to draw powder from the
receptacle, through the tube, and into the flowing airstream to
form the desired aerosol. Usually, at least two spaced-apart
discrete penetrations will be formed in the access surface prior to
coupling the inlet end of the feed tube with one of the
penetrations. The other penetration permits a separate stream of
fluidization air to enter the receptacle, fluidize the powder, and
sweep the receptacle of the fluidized powder to help assure that
substantially all powder (preferably at least 70%, more preferably
at least 80%, and still more preferably at least 90%) is removed
into the flowing air stream. The high pressure gas stream will be
generated by abruptly releasing a charge of pressurized gas through
a flow path which intersects with the outlet end of the feed tube
at an angle selected to both (1) induce sufficient fluidization air
flow through the feed tube to fluidize and transport powder in the
receptacle and (2) break up powder agglomerates which remain as the
powder exits from the outlet end of the feed tube. The gas pressure
prior to release will usually be at least about 15 psig (to achieve
sonic velocity), preferably being at least 20 psig, and more
preferably being in the range from 20 psig to 150 psig, and usually
being in the range from 40 psig to 80 psig. The expanded volume of
released gas (measured at standard temperature and pressure (STP)
of 14.7 psig and 20.degree. C.) will thus usually be in the range
from 2 ml to 25 ml, preferably being from 4 ml to 15 ml. Release of
the high pressure gas can be effected by a manual trigger or
optionally by sensing negative pressure resulting from the
patient's inspiration (i.e., can be breath-activated). As described
in detail below, the high pressure gas stream will combine with the
fluidization air stream at a volume ratio (measured at STP) in the
range from 1:2 to 1:4 (high pressure gas: fluidization air) to
produce the aerosol which is subsequently inhaled by the patient,
optionally after capture in a plume capture chamber.
[0029] The method may further comprise the step of capturing the
resulting discrete volume of aerosolized powder in a plume capture
chamber prior to subsequent inhalation by the patient. The patient
is then able to inhale the entire aerosolized dose from the
chamber, concurrently with and/or followed by inhalation of ambient
air which sweeps the capture chamber to further assure efficient
delivery of the powder with minimum losses. Inhalation of chase air
following the initial bolus of medication will drive the medication
deep into the alveolar regions of the lung where absorption will
occur. The method optionally further comprises advancing a
plurality of powder-containing receptacles past-the feed tube,
typically in the form of a strip or disk, so the powder can be
sequentially drawn and dispersed from each receptacle.
[0030] In another aspect of the method of the present invention,
discrete quantities of a powdered medicament may be sequentially
delivered from a receptacle or reservoir. In contrast with the
previously described methods, the receptacle will include an amount
of powdered medicament which is larger than that intended to be
delivered in any single bolus, usually containing an amount which
is sufficient for a large number of boluses, usually at least 5,
preferably at least 10, and frequently 20 or more. The method
comprises inserting the inlet end of the feed tube into the
receptacle and flowing a high pressure gas stream past an outlet
end of the feed tube to induce airflow from the receptacle through
the tube. The powdered medicament is thus entrained in the airflow
passing through the feed tube and combined with the high pressure
gas stream at an outlet end of the feed tube. The high pressure gas
stream can be repeatedly directed past the outlet end of the feed
tube while the inlet end remains within the "bulk" powdered
medicament receptacle.
[0031] Apparatus according to the present invention comprise a base
enclosure having a support for the powder-containing receptacle at
a fluidization location. The feed tube is mounted within the base
enclosure and a mechanism for reciprocating the receptacle relative
to the feed tube (or extending the feed tube relative to the
receptacle) is optionally provided. A source of compressed gas for
generating the high pressure gas is also provided, typically in the
form of a hand-actuated pump, an electric (usually
battery-operated) pump, a compressed gas container, a two-fluid
system, or the like. The aerosolized powder dosage may thus be
formed by reciprocating the receptacle relative to the feed tube so
that the inlet end of the tube enters the receptacle. The high
pressure gas stream is released while the tube is in or adjacent to
the receptacle, and the resulting low pressure region at the outlet
end of the feed tube draws fluidization air into the receptacle
(preferably from the plume capture chamber which subsequently
receives the aerosol, thus minimizing net air introduced from
outside the device) to fluidize and extract the powder outward from
the receptacle through the tube, and into the high velocity gas
stream to form the desired dispersion. Usually, the capture chamber
is disposed over and in-line with the outlet end of the feed tube
to contain the "plume" of powder aerosol and allow the plume to
quiesce prior to inhalation by the patient. The feed tube does not
have jets or ejector tubes within the flow path, and the clear,
undisrupted flow path reduces any tendency for the feed tube to
clog or otherwise lose dispersion efficiency. Using air from the
capture chamber as a source of fluidization gas is advantageous
since it reduces the total volume of "new" gas introduced to the
chamber, making capture of the dispersion gas stream (i.e., the
combination of the high pressure gas stream and the fluidization
air stream) easier. Such recycling of air from the capture chamber,
however, is not an essential feature of the present invention.
Fluidization air can also be obtained directly from outside the
device.
[0032] In a particular aspect of the apparatus of the present
invention, the receptacle will be supported in a mechanism for
advancing a continuous web (e.g. a strip or disk) which carries a
plurality of receptacles past the fluidization location. Usually,
the web advance mechanism includes a cartridge or carriage which
holds the web and which is reciprocatably mounted relative to the
feed tube so that the receptacles may be sequentially advanced
while the cartridge and tube are separated, and the tube thereafter
introduced into the receptacle by moving the cartridge and tube
together. Optionally, the receptacle lid or other single access
surface (i.e., a surface on one side of the receptacle) will be
pierced immediately prior to introduction of the feed tube, usually
using a separate piercing mechanism which pierces the lid as the
cartridge is reciprocated relative to the feed tube. Alternatively,
the access surface can be pierced simultaneously with the insertion
of the feed tube. In the latter case, the inlet end of the feed
tube will usually have a piercing structure and/or additional
piercing structures will be provided to form additional
penetrations for the entry of the fluidization air.
[0033] In a specific aspect of the apparatus of the present
invention, the piercing mechanism will produce at least two
spaced-apart holes in the lid, where one hole receives or engages
the feed tube and the other hole(s) permit entry of displacement
air to fluidize the powder and sweep the receptacle as powder is
withdrawn through the feed tube. A conduit or other path may also
be provided for directing air from the plume capture chamber back
to the receptacle in order to at least partially provide the
necessary displacement air. The hole for the feed tube may be
formed simultaneously with or at a different time from the
displacement air hole(s). For example, the displacement air hole(s)
could be formed at a piercing station disposed ahead of the
dispersion station with the feed tube hole formed at the dispersion
station, or vice versa. It also may be desirable to provide a
piercing mechanism at the dispersion station where the feed tube
piercing structure is reciprocated relative to the receptacle in a
separate motion from the displacement air hole piercing
structure.
[0034] The present invention further provides apparatus for
aerosolizing of powder comprising a feed tube having an inlet end,
an outlet end, and a lumen defining an axial flow path between said
inlet end and outlet end. At least one conduit is provided for
flowing a high velocity gas stream past the outlet end in a
direction which converges with the axial flow path at an angle in
the range from 12.5.degree. to 65.degree.. It has been found that
the angle of convergence in this range induces a sufficient flow of
fluidization air in the feed tube to efficiently empty an
associated powder receptacle (typically removing and aerosolizing
at least 80% and preferably at least 90% of the powder initially
present in the receptacle) while also providing sufficient shear
energy at the outlet end to substantially break up agglomerates
which are present in the powder.
[0035] The aerosolizing apparatus may include two or more separate
gas conduits which converge from different, usually opposite
(diametrically opposed), sides of the flow path. Alternatively, the
high pressure gas conduit may terminate in a single annular
aperture which circumscribes the outlet end of the feed tube and
which creates a gas flow path which converges on the axial flow
path. The latter approach however, will generally be less preferred
since it is difficult to manufacture annular apertures in the small
size required. The total lumen-area (A.sub.1) of the high pressure
(dispersion) gas flow conduit(s) will usually be in the range from
0.05 mm.sup.2 to 0.3 mm.sup.2, while the throat of the feed tube
immediately upstream of the gas conduit(s) tube will have a lumen
area (A.sub.2) in the range from 0.5 mm.sup.2 to 10 mm.sup.2. The
area (A.sub.3) and length of the mixing volume immediately
downstream from the high velocity gas conduits are preferably in
the range from the 0.6 mm.sup.2 to 11 mm.sup.2 and 0.5 mm to 3 mm,
respectively. The feed tube upstream of the throat will usually
have an area (A.sub.4) in the range from 0.6 mm.sup.2 to 15
mm.sup.2.
[0036] The aerosolizing apparatus may further include a diffuser
tube extending from the outlet end of the mixing volume and having
a lumen which is usually but not necessarily coaxially aligned with
the feed tube lumen. The diameter of the diffuser tube lumen will
increase in a direction away from the outlet end of the mixing
volume, typically diverging at a half angle of 2.degree. to
10.degree. over a length in the range from 0.5 cm to 5 cm, usually
having an outlet area which is about four times the inlet (mixing
volume) area. The diffuser tube thus causes a reduction in the
velocity of the gas stream exhausted from the outlet end of the
mixing volume, where velocity is at a maximum, prior to entering
the plume capture chamber. The plume continues to slow rapidly as
it expands within the chamber and approaches a quiet or quiescent
state prior to inhalation.
[0037] The present invention further provides a feed tube assembly
comprising a casing, a flow-directing member, and a feed tube. The
assembly is replaceable within the aerosol dispersion system,
facilitating removal and cleaning or exchange of the assembly if it
becomes plugged or fouled.
[0038] The invention provides an improved apparatus for
aerosolizing a powdered medicament. The apparatus is of the type
having a housing and a source of pressurized gas for aerosolizing
the powder. Such an apparatus is improved by providing a
pressurization cylinder, a piston slidable within the cylinder, and
a release valve in communication with the cylinder. Further
provided is a handle assembly having a handle operably attached to
the piston and a means for closing the valve. In this manner,
translation of the handle closes the valve and axially translates
the piston within the cylinder to produce the pressurized gas.
[0039] In one aspect, the release valve comprises a valve stem
connected to a valve poppet, and the means for closing the valve
comprises a roller cam adjacent the valve stem for translating the
valve stem to close the valve as the handle is translated radially
outward from the housing. In another aspect, the handle assembly
further includes a toggle link which moves over-center to hold the
roller cam against the valve stem and keep the valve closed. In
this way, the valve is held closed while the piston is translated
back toward the housing to produce the pressurized gas. In a
further aspect, the handle assembly includes a linkage between the
handle and the piston. In this manner, the linkage reciprocally
translates the piston between a retracted position and a charged
position within the cylinder as the handle is translated radially
outward and radially inward relative to the housing. With such a
configuration, the handle may be moved radially outward to both
close the valve and retract the piston, while inward movement of
the handle charges the cylinder with pressurized gas.
[0040] In yet another aspect, an interlocking means is provided for
preventing inward radial translation of the handle until the toggle
link has moved over-center to hold the valve closed. Preferably,
the interlocking means comprises a rack and a pawl. In a further
aspect, a release button is provided for translating the roller cam
from the over-center position to open the valve. In yet a further
aspect, the cylinder preferably includes a one-way valve for
allowing air to enter the cylinder as the piston is translated to
the retracted position.
[0041] In one particular aspect, the powdered medicament is held
within a receptacle. A feed tube is provided having an inlet end,
an outlet end, and a lumen extending therebetween so that the inlet
end may be inserted into the receptacle. In this way, compressed
gas exiting the release valve may be flowed past the outlet end of
the feed tube, with powder from the receptacle being extracted
through the tube and dispersed in the flowing compressed gas to
form the aerosol. Preferably, a means is provided for piercing at
least one hole in an access surface of the receptacle
simultaneously with inserting the inlet end of the feed tube into
the receptacle. In a preferable aspect, the piercing means
comprises a pair of pointed tabs, with the tabs being each disposed
at an oblique angle relative to the access surface of the
receptacle when the tabs are pierced through the access
surface.
[0042] In another particular aspect, a means is provided for
reciprocally translating the receptacle toward and away from the
piercing means. The translating means preferably includes an
over-center linkage for locking the receptacle in place upon
insertion of the inlet end of the feed tube into the receptacle. In
another aspect, a positioning pin is provided for aligning the
receptacle in a preferred orientation relative to the piercing
means while inserting the inlet end of the feed tube into the
receptacle.
[0043] In yet another particular aspect, the handle assembly
includes four linkages for attaching the handle to the housing. In
this manner, the handle may be translated radially outward and
radially inward relative to the housing with a generally constant
force, and with a more linear motion than with a simple pivot.
Further, such linkages reduce the distance that the handle must be
translated away from the housing, thereby making easier hand
operation of the handle assembly. In another aspect, a means is
provided on or in association with the housing for producing verbal
operating instructions.
[0044] The invention provides an exemplary apparatus for
aerosolizing a powder held in a receptacle having a puncturable
access surface. The apparatus includes a housing, a source of
pressurized gas, a capture chamber attached to the housing, and a
transjector assembly removably held within the housing. The
transjector assembly includes a means for piercing the access
surface of the receptacle and for receiving pressurized gas to draw
powder from the receptacle and into the capture chamber. In a
preferable aspect, the transjector assembly receives gas directly
from the gas source and delivers powder directly to the capture
chamber without powder passing through other portions of the
apparatus.
[0045] In a particular aspect, an interface seal is provided
between the transjector assembly and the housing so that
pressurized gas may be passed from the housing to the transjector
assembly without substantial loss of the gas. Preferably, the
interface seal is angled relative to a central axis of the
transjector assembly to facilitate easy removal of the transjector
assembly from the housing. In another aspect, a receptacle seal is
provided for forming a seal between the transjector and the
receptacle. In a further aspect, the transjector assembly is keyed
to be repeatedly received into the housing in a unique
orientation.
[0046] In another particular aspect, the capture chamber is axially
slidable over the housing so that the capture chamber may be placed
in a collapsed position substantially covering the housing or an
extended position forming an enclosure for receiving aerosolized
powder. Preferably, at least one detent is provided in the housing
and at least one notch is provided in the capture chamber, with the
detent being received into the notch when the capture chamber is in
the extended position. A spring is preferably provided for
outwardly biasing the detent. In another aspect, the detent is
generally V-shaped in geometry. In a further aspect, the capture
chamber comprises an elongate chamber body having at least one
elongate ridge or rib extending longitudinally along the body. The
elongate ridge engages the housing when the chamber is collapsed to
limit the amount of accumulated powder on the chamber that may be
scraped from the chamber by the housing. In yet another aspect, the
chamber body is asymmetrical in cross-sectional geometry and
includes a mouthpiece. A cap is preferably removably held over the
mouthpiece to prevent external dust and particulate from entering
the chamber and to hold the powdered medicament within the chamber
until ready to be inhaled. A seal is preferably provided between
the cap and the mouthpiece, with the seal preferably being
configured to function as a bleed valve to allow excess gas within
the chamber to escape.
[0047] The invention further provides a receptacle for holding a
powdered medicament, with the receptacle being adapted to be
received into a housing of an aerosolizing apparatus. The
receptacle includes a receptacle body having a puncturable access
surface and a tab extending from the receptacle body. In this
manner, the receptacle body may be received into an aperture in the
housing with at least a portion of the tab remaining outside the
housing. In one aspect, the tab includes a keyed hole adapted to
receive an alignment pin in the aerosolizing apparatus. By keying
the hole in the tab, the receptacle may be configured so that it
may only be used with an apparatus having a mating alignment pin.
In this way, the apparatus may be configured to receive only
certain receptacles having a particular medicament.
[0048] The invention provides an improved method for aerosolizing a
powdered medicament. The method is of the type wherein the powder
is entrained and suspended in a flowing gas stream and comprises
providing a housing having a pressurization cylinder, a piston
slidable within the cylinder, a release valve in communication with
the cylinder, and a handle for axially translating the piston and
for closing the release valve. The handle is initially translated
away from the housing to axially translate the piston within the
cylinder to a retracted position and to close the release valve.
The handle is then translated back toward the housing to translate
the piston to a position where it creates a charge of pressurized
gas. The valve is released following charging to abruptly discharge
the pressurized gas.
[0049] In one particular aspect, translation of the handle in the
direction of the housing is prevented until the release valve is
closed. In this way, premature introduction of gas to the
medicament is prevented until the cylinder is fully charged. In
another aspect, the release valve is held closed while translating
the handle back toward the housing so that gas in the cylinder may
be charged by the piston. In a further aspect, the handle is kept
generally parallel to the housing when translated. Preferably, the
handle is translated toward the housing to pressurize the gas while
applying a generally constant force to the handle.
[0050] In another particular aspect, the powder that is suspended
in the released gas is introduced into a capture chamber while
simultaneously bleeding off a preselected amount of gas from the
capture chamber. In still another aspect, a transjector assembly is
provided for receiving the pressurized gas and aerosolizing the
powder. The transjector assembly is removably held in the housing
so that it may periodically be removed from the housing for
cleaning. In yet another aspect, verbal operating instructions are
produced from the housing.
[0051] In still another particular aspect, a receptacle having a
puncturable lid is provided for holding the medicament. The
receptacle is translated toward the transjector assembly until the
transjector assembly penetrates the lid. Preferably,the receptacle
is guided toward the transjector so that the transjector penetrates
the lid at a known and a predictable position. The receptacle is
preferably held with the transjector assembly penetrating its lid
until after the valve is released.
[0052] The invention provides an exemplary method for aerosolizing
a powdered medicament. According to the method, receptacles are
provided having a receptacle body and a tab extending from the
receptacle body, with the powdered medicament being held within the
receptacle bodies. One of the receptacles is inserted into a
housing having an aperture, with the receptacle body being received
within the aperture so that at least a portion of the tab remains
outside the housing. The receptacle body is raised and
simultaneously pierced and the powdered medicament in the
receptacle is extracted in a gas stream that can be inhaled. The
receptacle is lower, and the tab is then pulled to remove the
receptacle from the housing.
[0053] In one aspect, the housing has a reciprocatable capture
chamber for receiving the powder-bearing gas stream, and the
chamber is preferably deployed prior to inserting the receptacle.
Deploying of the chamber exposes the aperture, and insertion of the
receptacle into the aperture prevents the chamber from retracting
until the receptacle is removed.
BRIEF DESCRIPTION OF THE DRAWINGS
[0054] FIG. 1 is a schematic illustration of an aerosol dispersion
system constructed in accordance with the principles of the present
invention.
[0055] FIG. 2 is a perspective illustration of a powder feed tube
assembly employed in the aerosol dispersion system of FIG. 1, shown
in quarter-section with its inlet end proximate a powder
receptacle.
[0056] FIG. 3 illustrates a preferred powder receptacle lid
penetration pattern.
[0057] FIG. 4A is a cross-sectional view of a portion of the feed
tube assembly illustrated in FIG. 2.
[0058] FIG. 4B is a cross-sectional view taken along line 4B-4B of
FIG. 4A.
[0059] FIG. 4C is an alternative cross-sectional view taken along
line 4B-4B of FIG. 4A.
[0060] FIG. 5 is a schematic illustration showing the relative
sizes and convergence angles of the feed tube lumen and dispersion
gas conduits of the present invention.
[0061] FIG. 6 illustrates a feed tube lumen in combination with a
dispersion gas conduit having an annular aperture which defines a
conical flow path.
[0062] FIG. 7 is a perspective view of an alternative feed tube
assembly constructed in accordance with the principles of the
present invention.
[0063] FIG. 8 is an exploded view of the feed tube assembly of FIG.
7.
[0064] FIG. 9 is a cross-sectional view of the feed tube assembly
of FIG. 7
[0065] FIG. 10 illustrates a third alternative feed tube assembly,
similar to that of FIG. 7-9, but further including self-penetrating
elements which permits entry of the feed tube and fluidization air
tubes into a powdered medicament receptacle.
[0066] FIG. 11A is an enlarged, detailed view of the
self-penetrating elements of FIG. 10.
[0067] FIG. 11B is an enlarged view of an alternative construction
of a self-penetrating element.
[0068] FIGS. 12A-12C illustrate use of the feed tube assembly of
FIGS. 7-9 in dispersing a powdered medicament from a single unit
dosage receptacle.
[0069] FIG. 13 is a perspective view of a particularly preferable
apparatus for aerosolizing a powdered medicament according to the
present invention.
[0070] FIG. 14 is a perspective view of the apparatus of FIG. 13
rotated 180 degrees and showing a capture chamber in a collapsed
configuration and a mouthpiece on the chamber.
[0071] FIG. 15 is an exploded perspective view of the apparatus of
FIG. 13 showing a transjector assembly for aerosolizing the
powdered medicament according to the present invention.
[0072] FIG. 16 illustrates the transjector assembly of FIG. 15
positioned over an exemplary receptacle for holding the powdered
medicament according to the present invention.
[0073] FIG. 17 is an exploded view of the transjector assembly of
FIG. 16.
[0074] FIG. 18 is a cross-sectional view of the transjector
assembly and receptacle of FIG. 16.
[0075] FIG. 19 illustrates penetration of the transjector assembly
of FIG. 19 into the receptacle.
[0076] FIG. 20 is a perspective view of the apparatus of FIG. 13
showing introduction of a receptacle having the powdered medicament
into the apparatus.
[0077] FIG. 20A is a top view of the receptacle being placed onto a
carrier of the apparatus of FIG. 13.
[0078] FIG. 21 is a cross-sectional side view of the apparatus of
FIG. 13.
[0079] FIG. 22 is a side view of the apparatus of FIG. 13 having
its outside cover removed.
[0080] FIG. 23 is a side view of a handle assembly along with other
selected components of the apparatus of FIG. 13, with the handle
assembly being shown in a closed configuration.
[0081] FIG. 24 is a more detailed view of selected components of
the apparatus of FIG. 23 and shows a release valve in an open
configuration.
[0082] FIG. 25 illustrates the handle assembly and other selected
components of FIG. 23, with the handle assembly being extended to
close the release valve and retract a piston according to the
present invention.
[0083] FIG. 26 is a more detailed view of the release valve of FIG.
25 shown in the closed position.
[0084] FIG. 27 is a perspective view of the release valve of the
apparatus of FIG. 13.
[0085] FIG. 28 is a cross-sectional view of the release valve of
FIG. 27 showing the valve in an open configuration.
[0086] FIG. 29 is a cross-sectional view of the release valve of
FIG. 27 with the valve being in a closed configuration.
DESCRIPTION OF THE SPECIFIC EMBODIMENT
[0087] Referring now to FIG. 1, a system 10 for dispersing a powder
medicament from a plurality of receptacles 12 by insertion of a
feed tube assembly 14 will be described. The receptacles may be in
any form that holds and preserves the medicaments and which
provides a puncturable access surface. As illustrated, receptacles
12 are in a continuous web comprising individual wells covered by a
puncturable lid, typically a metal foil or other conventional
laminate. Each receptacle will include a precise dosage of the
powdered medicament to be delivered. The amount of powder in each
individual receptacle will usually be in the range from about 1 mg
to 20 mg, more usually being from 2 mg to 10 mg. The continuous web
may be in the form of a strip, disk, or molded structure with a
closure. The manufacture of such containers, often referred to as
"blister packs" is well known in the pharmaceutical packaging art
and need not be described further.
[0088] Although illustrated with cartridge 22 in FIG. 1, it will be
appreciated that the powder dispersion systems of the present
invention could also be constructed to receive single dosage
packages carrying only one receptacle. In such a case, the user
would insert the package so that the receptacle was properly
oriented relative to feed tube 40 (FIG. 2) of feed tube assembly
14. Necessary piercings in the access surface of the receptacle
could be made manually prior to insertion, could be made within the
system 10 (either prior to or simultaneous with introduction of the
feed tube assembly 14) or could be preformed and exposed by peeling
away a cover prior to insertion of the package into the device.
Multiple receptacle packages could also be provided where the
package is inserted into the device at different orientations in
order to selectively expose individual receptacles to the feed
tube. A variety of design options are available when the user
inserts a single receptacle prior to each use.
[0089] The system 10 further comprises a base enclosure 11, and the
feed tube 40 (FIG. 2) of feed tube assembly 14 has an inlet end 16
and an outlet end 18. A pressurized gas source 20 is provided
within the base enclosure 11 and is connected to the proximal end
of the feed tube assembly 14 to provide a high pressure gas stream,
as will be described in greater detail in connection with FIG.
2.
[0090] The receptacles 12 will be mounted within the base enclosure
11 to reciprocate relative to the inlet end 16 of feed tube
assembly 14. Preferably, the strip of receptacles 12 will be
mounted within a cartridge 22 which is reciprocatably mounted in
the base enclosure 11, while the feed tube assembly 14 is fixedly
mounted within the base enclosure. In this way, the receptacles 12
may be sequentially advanced past a fluidization location (defined
by the inlet end 16 of feed tube assembly 14) within the cartridge
22, with the receptacle which is at the dispersion or fluidization
location being brought proximate the inlet end 16 of the feed tube
to permit emptying of its powdered contents, as described in more
detail hereinafter. Both reciprocation of the cartridge 22, and
advance of the receptacles 12 within the cartridge, may be
accomplished manually by the user. Alternatively, a mechanism may
be provided within the base enclosure 11 for simultaneously
reciprocating the cartridge 22 and advancing the strip of
receptacles 12, either as part of a manual advance mechanism. or as
part of a battery-powered mechanism.
[0091] In the embodiment of FIG. 1, penetrations will be formed in
the lid of the strip of receptacles 12 by a piercing mechanism 24.
As illustrated, the piercing mechanism 24 will be fixedly mounted
within the base enclosure 11 and will include a plurality of
sharpened penetrating elements 26 disposed to contact and penetrate
the puncturable lid 92 (FIG. 3) of the receptacles 12 when the
cartridge 22 is reciprocated, as illustrated in broken line in FIG.
1. The piercing mechanism 24 will be located to contact a
receptacle 12 which is located one station prior to the feed tube
assembly 14. Thus, each receptacle 12 will be pierced immediately
prior to being advanced to the fluidization location.
[0092] It will be appreciated that a wide variety of mechanisms can
be provided for piercing holes within the lid of each receptacle
and for bringing the receptacle into proximity with the feed tube
assembly 14. For example, the cartridge 22 could be held stationary
within the base enclosure 11 while each of the feed tube assembly
14 and piercing mechanism 24 could be reciprocated, either together
or separately. Alternatively, the inlet end 16 of the feed tube
assembly 14 could be configured to be self-penetrating (see FIGS.
10 and 11A and 11B below). In the latter case, the desired pattern
of penetrations would be formed in the puncturable lid of the
receptacle 12 at the same time that the inlet end is engaged
against or inserted into the interior of the receptacle. The
present invention is not limited to any particular puncturing and
advance mechanisms which might be employed.
[0093] The gas source 20 will provide a volume of high pressure air
or other gas to the outlet end 18 of the feed tube 40 (FIG. 2) of
feed tube assembly 14 in order to induce a flow of fluidization
air, draw powder from the receptacles 12, and disperse the powder
within the flowing gas stream. While the high velocity air from the
gas source will usually be directed past the outlet end 18, it will
be appreciated that feed tube 40 could be extended past the high
velocity gas stream inlet point, for example by providing side
inlets in an elongate tube. Thus, the high velocity gas could
actually combine with the fluidization air carrying the entrained
particles within the feed tube itself. With such a construction,
the feed tube 40 could define the mixing volume 60 (FIG. 4A), as
described below.
[0094] The gas source 20 will provide gas at a relatively high
pressure, usually being sufficient to provide for sonic flow past
the outlet end 18 of the feed tube assembly 14, typically being
above 15 psig, usually being at least 20 psig, and preferably being
in the range from 20 psig to 150 psig, and most preferably being in
the range from 40 psig to 80 psig. The energy stored in the charge
of high pressure gas will be sufficient to induce air flow through
the feed tube 40 of feed tube assembly 14 which in turn draws
fluidization air into the receptacle to fluidize and extract the
expected weight of powdered medicament from the receptacle 12. The
expanded volume of the charge will typically be in the range from
about 2 ml to 25 ml (measured at STP), usually being in the range
from about 4 ml to 15 ml. The volume of fluidization gas whose flow
is induced through the feed tube assembly 14 by the high velocity
gas stream will usually be from 2 ml to 100 ml, preferably from 4
ml to 60 ml, measured at STP. The specific manner in which the high
pressure gas is flowed past the outlet end 18 of feed tube assembly
14 will be described in greater detail in connection with FIG.
2.
[0095] Gas source 20 may be in the form of a manual pump, an
electric pump, a high pressure gas cylinder, or the like. The
construction of manual pumps in hand-held powder dispersion devices
is described in the patent and technical literature. See e.g.,
WO90/07351. The construction of electric gas pumps, gas cylinder
supplies, and two-fluid systems is also well within the skill in
the art.
[0096] The gas dispersion system 10 further includes a plume
capture chamber 30 which is disposed over the outlet end 18 of feed
tube assembly 14 in order to capture powder released from the tube.
The plume chamber 30 will include a mouth piece 32 at its distal
end and will have an internal volume sufficient to capture
substantially all of the powder dispersion which is delivered from
the feed tube assembly 14. Usually, the volume will be in the range
from 50 ml to 1000 ml, preferably from 100 ml to 750 ml. The
chamber 30 will also include an ambient air inlet (not shown),
optionally a tangential inlet as described in co-pending
application Ser. No. 07/910,048, the full disclosure of which is
incorporated herein by reference. Alternatively, the air inlet can
be axial or spiral, as described in connection with FIGS. 7-9,
below.
[0097] In operation, the powder dispersion will be introduced into
the plume capture chamber 30, as illustrated by arrows 34. Air will
be displaced through the mouthpiece 32, and optionally back through
an annular lumen in the feed tube assembly 14, as indicated by
arrows 36 and as will be described in more detail in connection
with FIG. 2. Such recycling of air from the plume capture chamber
30 as the fluidization gas enters greatly reduces the total volume
of new gas being introduced to the system. The only new gas
introduced (prior to patient inhalation) will be from the gas
source 20. After the entire contents of a receptacle 12 has been
dispersed and captured within the plume chamber 30, the patient
will inhale the entire aerosolized dose through the mouthpiece 32
chased by ambient air through the chamber to extract all
aerosolized medicament from the chamber. optionally, an orifice
plate or other flow limiting element may be placed in the chamber
air inlet path to slow inhalation and enhance the penetration depth
of the powder particles. Inhalation of the additional air further
assures that the powdered medicament will be efficiently dispersed
and driven deeply into the alveolar regions of the lung where it is
available for systemic absorption or localized delivery.
[0098] Referring now to FIG. 2, the feed tube assembly 14 includes
an inner tubular feed tube 40 which defines the inlet end 16 of the
feed tube assembly 14 at its distal end and an outer coaxial tube
member 42 which defines an annular lumen 44 for passing return air
from chamber 30 back to the receptacle 12, as described in more
detail hereinafter.
[0099] Lumen 46 of the inner tubular feed tube 40 extends from the
inlet end 16 to the outlet end 18 where a throat or constriction is
optionally formed. The throat or constriction is not necessary for
operation of the feed tube assembly 14, but it is the area
(A.sub.2) at the outlet end of the lumen 46 (FIG. 4A) which
determines the performance characteristics of the feed tube, as
described in more detail hereinafter. Dispersion gas from gas
source 20 enters the feed tube assembly 14 through a port 50
connected to an annular plenum 52. The annular plenum 52, in turn,
is connected to a pair of gas conduits 54 which direct converging
gas streams into the flow path defined by lumen 46 of the feed tube
40. The angle at which the gas conduits 54 are oriented is chosen
to provide a proper balance between the magnitude of the flow
velocity induced in the powder stream drawn through lumen 46 and
the magnitude of the shear forces which break up agglomerates in
the powder as they pass from the outlet end 18 into an expansion
section 58.
[0100] The area (A.sub.2) (FIG. 4A) of the throat 18 of the feed
tube lumen 46 will typically be in the range from 0.5 mm.sup.2 to
10 mm.sup.2, preferably being in the range from 1 mm.sup.2 to 4
mm.sup.2. In the illustrated embodiment, area (A.sub.4) of the
upstream portion of lumen 46 (FIG. 4A) is greater than A.sub.2,
typically being from 0.6 mm.sup.2 to 15 mm.sup.2. The upstream
lumen 46, however, could have a uniform area along its entire
length equal to the outlet end area (A.sub.2), although such a
construction would be less preferred.
[0101] Referring to FIG. 4A, a mixing volume 60 having a uniform
(non-expanding) cross-sectional area (A.sub.3) and a length
(L.sub.2) is located immediately at the outlet end 18 of the feed
tube 40. The cross-sectional area (A.sub.3) is shown to be slightly
larger than feed tube throat area( A.sub.2) outlet, but this is not
necessary. The exemplary area( A.sub.3) is typically in the range
from 0.6 mm.sup.2 to 11 mm.sup.2. The length (L.sub.2) is 1-5 times
the diameter of the mixing volume 60 (for circular cross-sections),
typically being in the range from 0.5 mm to 2 mm. In the
illustrated embodiment, a pair of gas conduits 54 (FIG. 4B) are
shown, as illustrated in FIG. 4B. It would also be possible to
utilize only a single inlet jet or to provide three, four or more
separate inlets, with four inlets 54' being as illustrated in FIG.
4C. Other configurations will also be usable including a continuous
annular aperture, as described in connection with FIG. 6, or
combinations of perpendicular jets (to break-up agglomerates) and
axially directed jets (to induce fluidization gas flow).
[0102] Referring now to FIG. 5, high pressure gas conduits 72 are
arranged around the throat of a feed tube lumen 70 at angles
.alpha..sub.1, and .alpha..sub.2, which will usually but not
necessarily be equal. The angles .alpha. are important to achieving
both adequate mass transfer of powder from the receptacle and
adequate "agglomerate break up" as the powder enters the mixing
volume immediately downstream from the outlet orifices of the
conduits 72. The angles a will be in the range from 12.5.degree. to
65.degree., preferably being from 25.degree. to 40.degree..
[0103] It will be appreciated that the high pressure gas lumens 72,
as illustrated in FIG. 5, may be formed as a single conical plenum
80 terminating in an annular aperture 82, as illustrated in FIG. 6.
The angle of convergence .alpha. will generally be within the range
set forth above for .alpha. above, and the total area of the
annular lumen 82 will generally be within the total area A.sub.2
for the high pressure gas lumens also set forth above. Typically,
the conical plenum 80 will have a width w in the range from about
0.005 mm to 0.1 mm.
[0104] Referring again to FIG. 2, the feed tube assembly 14
operates by coupling the inlet end 16 of the feed tube 40 with an
aperture 90 (FIG. 3) formed into lid 92 over a receptacle 12. As
illustrated, the inlet end 16 is inserted through the lid 92 and
into the receptacle 12, but is will also be feasible to engage the
inlet end over the aperture 90, typically utilizing a sealing
gasket as illustrated in FIGS. 7-10, below. The aperture 90 will be
surrounded by space-apart apertures 94 (illustrated as six) which
allow for the entry of fluidizing air as entrained powder is
extracted through the inner feed tube 40. The aperture 90 is shown
to be centered, but that is not necessary. In a preferred aspect of
the present invention, at least a portion (and preferably all) of
the fluidizing air will be provided through the annular lumen 44
via a port 96 in the feed tube assembly 14 disposal at the bottom
of the interior of the plume chamber 30. Such "recycled" air from
the plume chamber 30 passes through an annular plenum 98 from the
port 96 into the annular lumen 44. Optionally, a rubber flange or
skirt 95 may be provided to prevent loss of fluidizing air from the
lumen 44 to the receptacle 12. The recycling of fluidization air
from the plume chamber 30 helps contain the plume of dispersed
powder within the plume chamber since it limits the amount of air
which is displaced and expelled through the mouthpiece 32 or other
opening in the chamber.
[0105] Introduction of the inlet end 16 of feed tube 40 of the feed
tube assembly 14 into the receptacle 12 is advantageous (but not
necessary) since it facilitates substantially complete removal of
powder (usually at least 80% and preferably at least 90% by weight)
from the interior of the receptacle. Such complete removal is
further enhanced by the entry of fluidization air through the
space-apart apertures 94, which creates an air flow pattern which
can sweep powder from all corners of the receptacle into the
dispersion lumen 46.
[0106] An alternative embodiment of a feed tube assembly 100 is
shown in FIGS. 7-9. The feed tube assembly 100 is generally
functionally equivalent to the feed tube assembly 14 and can be
used in place thereof in the system of FIG. 1. The feed tube 100,
however, is particularly suitable for fabrication from molded
plastic parts, or from a combination of molded plastic and
fabricated metal parts.
[0107] Feed tube assembly 100 comprises a casing 102, a gas
flow-directing cone 104, a feed tube element 106, an end piece 108,
a flexible valve element 110, and an end gasket 112. The feed tube
element 106 is received in an open cavity 114 disposed in a lower
end of the flow-directing cone 104. The flow passages within feed
tube 106 will generally be the same as that described previously
for feed tube assembly 14, and feed tube assembly 100 further
includes a mixing volume 116 located immediately above the open
cavity 114 and an expansion region 118 located above the mixing
volume. The dimensions of the mixing volume 116 and expansion
region 118 will generally be the same as those described previously
in connection with the feed tube assembly 14.
[0108] As best seen in FIG. 8, the flow directing cone 104 may
include a plurality of air flow channels 120 formed over its
exterior surface. Usually, there will be from 1 to 10 channels,
having a total cross-sectional area from 5 mm.sup.2 to 150
mm.sup.2, preferably from 40 mm.sup.2 to 100 mm.sup.2. The air flow
channels 120 are shown in a generally spiral pattern in FIG. 8. The
spiral pattern may be preferred since it will impart a vortical
flow to replacement air entering the associated plume chamber as
the patient inhales. The airflow channels 120, however, could also
have a generally straight configuration which would impart a
conically expanding, but not spiral, flow pattern to the
replacement air. It would also be possible to employ air flow
channels which are straight and parallel to each other to impart a
general axial replacement airflow pattern into the plume chamber.
It will also be possible to employ a single annular opening by
using pins of other non-dividing elements for supporting the
flow-direction cone, where the cone may have a continuous surface
without discrete channels.
[0109] The airflow channels 120 are enclosed at their outward
extremities by the inner surface 122 (FIG. 9) of the casing 102.
The air flow channels thus extend from a lower end 124 to an upper
end 126, providing flow paths for replacement or "chase" air into a
plume chamber, as described in more detail below. The flow paths
provided by air channels 120 will also provide for recycling of air
in the reverse direction from the plume chamber to an associated
powder receptacle when the powder is being fluidized. This function
will be described in more detail below.
[0110] The end piece 108 includes a plurality of air flow apertures
126 located around a central opening 128. The flexible valve 110
lies over the air flow apertures 126 and is secured between the
lower end of casing 102 and the upper surface of the end piece, as
best seen in FIG. 9. The flexible valve element 110 generally acts
as a one-way valve, permitting entry of air from the outside of the
feed tube assembly 100 into the region formed between the lower end
of casing 102 and the end piece 108.
[0111] High pressure air will be able-to enter the open cavity 114
formed at the outlet end of feed tube element 106 through an inlet
port 130 formed in the casing 102 (FIG. 7). For simplicity, the
flow path from port 130 to the cavity 114 is not shown in FIG. 9.
Supply of high pressure gas to the cavity 114 acts to induce the
flow of fluidization air through the central lumen of the feed tube
element 106 in a manner completely analogous to that described
previously for feed tube assembly 14.
[0112] Referring now to FIGS. 10 and 11A, a modification of the
feed tube assembly 100 which permits direct penetration of a
medicament receptacle lid is shown. For convenience, all elements
which correspond to those shown in FIG. 7-9 will be numbered
identically. A feed tube penetrating element 140 is disposed at the
lower end of the feed tube 106. As shown in detail in FIG. 11, the
penetrating element 140 includes a pair of crossing internal walls
142 which terminate in a pointed blade structure 144. The blade
structure 144 leaves four separate flow passages 146 arranged in
quadrants within the feed tube 104. The flow passages 146 may
optionally stop beyond the attachment point of the blade structure
144 to the inside wall of the host tube.
[0113] A plurality of similar penetrating structures 150 are
provided for both piercing the receptacle lid and simultaneously
providing fluidization air inlet paths. The penetrating structures
150 may be provided in a carrier plate 152 or similar supporting
structure. The penetrating structures 150 will have a similar
conical blade structure to that described previously for the feed
tube penetrating structure 140. Thus, the structure of FIG. 10 can
provide for both the feed tube penetration and the peripherally
arranged fluidization air penetrations in the penetrable lid of a
medicament receptacle in a single motion where the lid is drawn
against the gasket 112 of the feed tube assembly 100.
[0114] FIG. 11B illustrates an alternative penetrating structure
151 formed by machining the end of a tube along two converging
planes. The resulting pointed elements are then pressed together to
form the structure having openings 153. The penetrating element 151
is advantageous since it peels back the lid as it is penetrated,
leaving the openings 153 clear to receive powder. The penetrating
structure 151 could be fabricated from molded plastic as well as
machined metal.
[0115] Referring now to FIGS. 12A-12C, use of the feed tube
assembly 100 of FIGS. 7-9 will be described in more detail.
Initially, a medicament receptacle R having preformed feed tube and
fluidization air penetrations 200 and 202 is engaged against the
gasket 112, as illustrated in FIG. 12A. Gasket 112 provides a seal
against penetrable lid 204 of the receptacle R. The inlet end of
feed tube 106 is shown to penetrate the lid 104, but it will be
appreciated that such penetration is not essential since a seal
will be provided by the gasket 112. Penetration may be desirable,
however, since the lid flaps which surround the penetration 200
will be held open.
[0116] After the receptacle R is in place, a burst of high pressure
air is introduced into the open cavity 114, as shown in FIG. 12B.
The high pressure air flows past outlet end of the feed tube 106,
inducing a flow of fluidization air through the receptacle R. In
particular, fluidization air is drawn through the air flow channels
120 from the overlying plume chamber (not illustrated), as shown by
arrows 210. The air drawn in through the air flow channels 120
enters the receptacle through penetrations 202, thus fluidizing the
powder and drawing the powder out through the feed tube 106. The
air flow through the feed tube thus entrains the powder and
combines the powder with high pressure gas flow at the outlet end
of the feed tube. The combined powder, fluidization air, and high
pressure dispersion gas is then introduced into the plume chamber,
as shown by arrows 212.
[0117] After the powder has been dispersed, patient will inhale
from the plume chamber which will cause a reverse flow of air
through the air flow channels 120, as illustrated in FIG. 12C,
ambient air will enter the central opening 128 through apertures
126 as the flexible valve element 110 opens. The air which enters
through apertures 126 will primarily pass through the air flow
channels 120. A portion, however, may pass back into the receptacle
R and upward through the feed tube into the plume chamber. Such
flow through the receptacle will further empty the receptacle of
any powder which may remain.
[0118] Referring to FIG. 13, a particularly preferable embodiment
of an aerosolizing apparatus 300 will be described. The apparatus
300 includes a housing 302 and a capture chamber 304 that is
slidable over the housing 302. Removably held within the housing
302 is a transjector assembly 306. The transjector assembly 306 is
similar to the feed tube assembly 100 as shown in FIGS. 7-9 and is
employed to introduce aerosolized medicament into the capture
chamber 304 as described in greater detail hereinafter. The
apparatus 300 further includes a handle assembly 336 having a
handle 338 that in combination with the transjector assembly 306 is
employed to aerosolize the medicament and will be described in
greater detail hereinafter. The housing 302 further includes an
aperture 340 for receiving a receptacle 342 (see FIG. 20) having
the powdered medicament.
[0119] The capture chamber 304 is sized to be slidably received
over the housing 302 so that the capture chamber 304 may be removed
from the housing 302 for cleaning and also so that chamber 304 can
be translated between a deployed position (see FIG. 20) and a
retracted position (see FIG. 14). In the deployed position, the
capture chamber 304 forms an enclosure for receiving aerosolized
medicament introduced by the transjector assembly 306 so that it
may be inhaled by a patient. Following inhalation, the capture
chamber 304 can be slid over the housing 302 to the retracted
position for storing. To hold the capture chamber 304 in the
retracted and the deployed positions, two pairs of detent pins 308
and 310 are provided. The detent pins 308, 310 are received into
slots 312 and 314 in the housing 302. Springs 316 and 318 are
preferably provided to outwardly bias the detent pins 308, 310. The
capture chamber 304 includes a chamber body 320 having a bottom
portion 322 and a top portion 324. Included in the bottom portion
322 are a pair of grooves (not shown) for engaging the detent pins
308, 310. The detent pins 308 are received in the grooves when the
capture chamber 304 is in the deployed position, and the detent
pins 310 are received into-the grooves when the capture chamber 304
is in the retracted position. The detent pins 308 and 310 each
include a V-shaped portion 326 and 328 for engaging the grooves in
the bottom portion 322 of the capture chamber 304. The particular
angle and orientation of the V-shaped portions 326 and 328 can be
varied to increase or decrease the amount of force required to
deploy or retract the capture chamber 304. The mating grooves on
the chamber 204 may also be provided with different angles to
assist in achieving this effect. Usually, the detent pins 310 will
be configured so that it is easier to translate the chamber 304
downward toward the bottom of the housing 302 than to translate the
chamber 304 upward toward the top of the housing 302. In this
manner, the chamber 304 may be placed in the retracted or storage
position with a relatively small force, while a relatively greater
force will be required to retrieve the chamber 304 from the storage
position. In this way, the chamber 304 will be configured to not
inadvertently slide open during non-use. In a similar manner, the
detent pins 308 will usually be configured so that a greater force
is required to altogether remove the chamber 304 from the housing
302 than to slide the chamber 304 down over the housing toward the
detent pins 308. In this way, inadvertent removal of the chamber
304 will be prevented when sliding the chamber 304 to the deployed
position.
[0120] The capture chamber 304 is preferably asymmetrical in
cross-sectional geometry so that the capture chamber 304 may be
repeatedly placed over the housing 302 at a known orientation. This
is particularly advantageous in insuring that an inhalation port
330 of a mouthpiece 331 (see FIG. 14) is properly positioned
relative to a fire button 418 (see FIG. 21) that is employed to
introduce the powdered medicament into the capture chamber 304. In
another aspect, the chamber body 320 will preferably include at
least one elongate ridge 324 extending longitudinally along the
length of the interior of the chamber body 320. The ridge 334 is
provided to contact the housing 302 and to keep the remainder of
the chamber body 320 spaced-apart from the housing 302 when the
capture chamber 304 is translated to the retracted position. Often,
residual powder will remain on the interior walls of the chamber
body 320 after use. As the chamber body 320 is slid over the
housing 302 to retract the capture chamber 304, the ridge 334
contacts the housing 302 to limit the amount of residual powder
that is scraped from the chamber body 320 by the housing 302.
Extensive scraping of the accumulated powder from the walls of the
chamber body 320 is undesirable in that the scraped powder may
become agglomerized and may interfere with the subsequent operation
of the apparatus 320. In a further aspect, a raised portion 335 is
provided on the housing 302 to insure a proper fit between the
bottom portion 322 and the housing 302.
[0121] The chamber body 320 is preferably constructed of a
transparent material and will usually be constructed of plastic.
Optionally, the plastic may be an inherently conductive polymer
such as that described in U.S. Pat. Nos. 5,342,889, 5,348,995, and
4,719,263, the disclosure of which is herein incorporated by
reference, to limit the amount of electric charge built up on the
walls of the chamber body 320 during use.
[0122] Referring to FIG. 14, the capture chamber 304 is shown in
the retracted position and will be used to describe operation of
the inhalation port 330 in greater detail. The capture chamber 304
includes a cover 344 that may be closed over the inhalation port
330. The cover 344 is employed to prevent external dust or
particulate from entering into the interior of the capture chamber
304 during storage and also to hold the aerosolized medicament
introduced by the transjector assembly 306 within the chamber 304
until ready for inhalation. Optionally, the cover 344 may include
seal 346 which is received over the inhalation port 330 when the
cover 344 is closed. When introducing the aerosolized medicament,
the pressure within the capture chamber 304 is increased. The seal
346 serves as a bleed valve to allow some of the pressurized gas
within the chamber 304 to spontaneously escape. Reducing the
chamber pressure in this manner is advantageous in preventing a
"puff" of medicament from escaping when the cover 344 is lifted for
inhalation.
[0123] The capture chamber 304 will preferably define an enclosed
volume of about 50 ml to 750 ml, and more preferably at about 100
ml to 250 ml. When the aerosolized medicament is introduced into
the chamber 304, the pressure inside will increase over ambient in
proportion to the amount of net gas exhausted into the chamber and
the volume of the chamber as dictated by Boyles' law where
P.sub.1V.sub.1=P.sub.2V.sub.2, T=constant at equilibrium. For
example, 8 ml of gas introduced into a 210 ml chamber will amount
to a pressure rise of about 0.6 psi. Thus, it is desirable for the
seal 346 to allow approximately 8 ml of gas to escape to drop the
pressure by 0.6 psi. The seal 346 is preferably constructed of
silicone, urethane or similar flexible elastomers, although a
similar functioning valve could be achieved with a spring loaded
rigid valve element such as a thin mylar or metal petal or
plate.
[0124] Referring to FIG. 15, placement of the transjector assembly
306 into the housing 302 will be described in greater detail. The
housing 302 includes a cylindrical opening 348 that is sized to
receive the transjector assembly 306. The opening 348 includes a
keyed slot 350 for receiving a keyed portion 352 of the assembly
306. The keyed slot 350 is provided so that the transjector
assembly 306 may be repeatedly placed in a known orientation when
the transjector assembly 306 is inserted into the opening 348. A
locking nut 354 is provided to secure the transjector assembly 306
into the opening 348. The locking nut 354 includes a pair of tabs
356 to allow for easier rotation of the nut 354 when securing or
unlocking the nut 354. To remove the transjector assembly 306, the
nut 354 is unscrewed and removed, and the transjector assembly 306
is lifted from the housing 302. Alternatively, the nut 354 may be
configured to snap fit into the opening 348 to hold the transjector
assembly 306 in place.
[0125] Referring to FIGS. 16 and 17, construction of the
transjector assembly 306 along with the receptacle 342 will be
described in greater detail. As best shown in FIG. 17, the
transjector assembly 306 includes a casing 358, a gas flow
directing cone 360, a feed tube element 362, an end piece 364, a
flexible valve element 366, and an end gasket 368. The transjector
assembly 306 operates substantially identical to the feed tube
assembly 100 as shown in FIGS. 7-9 in extracting and aerosolizing
the powdered medicament in the receptacle. The transjector assembly
306 differs from the feed tube assembly 100 in that the transjector
assembly 306 includes an alternative penetrating element 370 and a
pair of penetrating structures 372. The penetrating element 370 is
disposed at the lower end of the feed tube 362 and is employed to
extract powder from the receptacle 342 as previously described in
connection with the feed tube assembly 100 when the penetrating
element 370 is introduced into the receptacle 342. The penetrating
structures 372 are provided for both piercing the receptacle lid
and simultaneously providing fluidization air inlet paths. A
particular advantage of the penetrating structures 372 is that they
are easy to manufacture, thereby reducing the overall cost of the
transjector assembly 306. As best shown in FIGS. 21, 23 and 24, the
penetrating structures 372 may optionally be provided with a
plurality of points rather than a single point to facilitate
penetration into the receptacle lid.
[0126] As best shown in FIGS. 18 and 19, the receptacle 342
includes a receptacle body 374 having a penetrable lid 376 covering
an enclosure 378 and a tab 380. Within the tab 380 is a hole 382
for aligning the receptacle 342 with the transjector assembly 306
as described in greater detail hereinafter.
[0127] To penetrate the lid 376, the receptacle 342 is lifted (or
the transjector 306 is lowered) until the penetrating element 370
and the penetrating structures 372 pierce the lid 376 as shown in
FIG. 19. The penetrating structures 372 are angled relative to the
penetrating element 370 and operate similar to can openers to peel
back a portion of the lid 376 and form the air inlet paths. Once
the receptacle 342 is in place, a burst of high pressure air is
introduced into an open cavity 384 which flows past the outlet end
of the feed tube 362 to draw the powdered medicament within the
receptacle 342 through the transjector assembly 306 in a manner
similar to the feed tube assembly 100 described in FIG. 12-12C.
When the penetrating element 370 and the penetrating structures 372
pierce the lid 376, the end gasket 368 contacts the receptacle body
374 and forms a seal against the receptacle 342.
[0128] Referring to FIGS. 20 and 20A, placement of the receptacle
342 into the aperture 340 will be described in greater detail. The
receptacle 342 is delivered into the aperture 340 by grasping the
tab 380 and inserting the receptacle body 374 into the aperture 340
until stop shoulders 375 on the receptacle body 374 engages guide
pins 377 (see also FIG. 21) on which a carrier 442 (see also FIG.
22) rides and prevents further translation. At this point, the hole
382 is generally aligned with a pin 386. The receptacle 342 is then
lifted within the aperture 340 until the hole 382 is received over
the pin 386 which guides and aligned the receptacle 342 until
engaging the end gasket 368 (see FIG. 19). At all times, the tab
380 remains outside the housing 302. In this way, premature closure
of the capture chamber 304 is prevented since the tab 380 will
prevent retraction of the capture chamber 304. The tab 380 thus
ensures that the capture chamber 304 will always be in the deployed
position when the receptacle 342 is loaded into the apparatus 300.
Thus, the capture chamber 304 must always be in the deployed
position for the receptacle 342 to be loaded into the apparatus
300. Optionally, the pin 386 may be keyed to fit only a specific
hole configuration in the receptacle 342. In this manner, the
apparatus may be configured to receive only specific receptacles
having a given medicament. Alternatively, a plurality of pins and
corresponding holes in the receptacle may be provided to key the
apparatus 300.
[0129] Referring to FIGS. 21-27, operation of the apparatus 300 to
produce an aerosolized medicament will be described. As shown in
FIG. 21, the handle 338 on the handle assembly 336 is operably
connected to a piston 388 that in turn is translatably held within
a cylinder 390. A linkage 392 is provided to connect the piston 388
to the handle 338. As best shown in FIGS. 25 and 26, as the handle
338 is moved radially outward away from the housing 302, the
linkage 392 is pulled from the cylinder 390 to lift the piston 388.
When the handle 388 is fully extended (FIG. 25), the piston 388 is
in a retracted position. As the handle 338 is translated back
toward the housing 302, the piston 388 is translated within the
cylinder 390 to pressurize the gas within the cylinder 390. As best
shown in FIG. 21, the cylinder includes a one-way valve 394 that is
held within a retainer 396. The one-way valve 394 is preferably a
"duck bill" type valve which allows air into the cylinder 390 as
the piston 388 is translated to the extended position. When the
handle 338 is closed, the valve 394 is closed to prevent air from
escaping from the cylinder 390 through the valve 394. Pressurized
air from the cylinder 390 is passed via a transfer or an outlet
tube 398 (see FIGS. 21 and 25) to a release valve assembly 400.
[0130] The release valve assembly 400 is in turn in communication
with the transjector assembly 306 so that pressurized gas may be
supplied to the open cavity 384 as previously described in FIG. 19.
A seal 402 is provided between the valve assembly 400 and the
transjector assembly 306 to prevent high pressure air supplied from
the valve assembly 400 from escaping between the interface between
the valve assembly 400 and the transjector assembly 306. The seal
402 is preferably constructed of urethane, silicone, or a similar
elastomer, and is angled relative to a longitudinal axis of the
transjector assembly 306. In this way, the transjector assembly 306
may easily be inserted and removed to and from the housing 302
while at the same time allowing for a sufficient interface
seal.
[0131] The valve assembly 400 includes a valve stem 404 and a valve
poppet 406 for selectively preventing air from flowing through the
assembly 400 and will be described in greater detail hereinafter
with reference to FIGS. 27-29. In FIGS. 21-24, the valve assembly
400 is shown in the open position, with the poppet 406 being
unseated. In such a configuration, gas within the cylinder 390 will
not be significantly compressed upon translation of the piston 388
since air within the cylinder 390 will escape through the outlet
tube 398. When the valve assembly 400 is closed, air is prevented
from escaping from the outlet tube 398 so that only a "full stroke"
of air within the cylinder 390 may be compressed. In a particularly
preferable aspect of the invention, the apparatus 300 is configured
to close the valve assembly 400 as the piston 388 reaches the
extended position so that air within the cylinder 390 may be
compressed when the handle 338 is translated back toward the
housing 302. To close the valve assembly 400 in this manner, the
handle assembly 336 includes a linkage 408 (see FIG. 22) having
rack 410 securely attached thereto. The rack 410 includes an
elongate slot 412 for receiving a valve reset link 414 (see FIGS.
21 and 24). As best shown in FIGS. 21 and 24, the reset link 414 is
pivotally attached to a roller cam 416. In turn, the roller cam 416
is pivotally attached to a valve release button 418.
[0132] As best shown in FIGS. 25 and 26, as the handle 338 is
translated away from the housing 302 and as it reaches the fully
extended position, the linkage 408 pivots about a pin 420 causing
the reset link 414 to slide within the slot 412 until reaching a
left-hand end of the slot 412. At this point, the reset link 414 is
translated in the direction of the handle 338 to pivot the roller
cam 416 about pin 422. Further translation of the handle 338 causes
the roller cam 416 to lock over center. As the roller cam 416
toggles over center, the release button 418 is translated outward
from the housing 302 and the valve stem 404 is driven upwards by
the roller to seat the poppet 406 against a seat 452 (see FIG. 29),
thereby closing the valve assembly 400. At the same time, the
piston 388 is translated via linkage 392 to the extended position.
As the handle 338 is translated back toward the housing 302, the
reset link 414 slides within the slot 412 while the cam 416 remains
over center to keep the valve assembly 400 closed. At the same
time, the piston 388 is translated within the cylinder 390 to
compress the air within the cylinder 390. When the operator is
ready to produce the aerosolized medicament in the capture chamber
304, the release button 418 is depressed to move the cam 416 from
over center and allow the valve assembly 400 to be opened.
[0133] In one particular aspect, the apparatus 300 may be
configured to prevent translation of the handle 338 back toward the
housing 302 until the handle 338 is fully extended to place the cam
416 over center and close the valve 400. To restrict movement of
the handle 338 in this manner, the handle assembly includes an
interlock pawl 424 (see FIG. 22) for engaging ratchet teeth 426 on
the rack 410. As the handle 338 is extended to pivot the cam 416
about pin 422, the pawl 424 engages the teeth 426 of the rack 410
to prevent closure of the handle 338 until the cam 416 moves over
center to close the valve assembly 400. An interlock pawl spring
425 is provided to bias the pawl 424 against the ratchet teeth 426
until the cam 416 is over center. In this way, pumping of the
handle 338 is prevented which would prematurely deliver air into
the transjector assembly 306. Such premature delivery is
undesirable if the user has already loaded and punctured the
receptacle. Alternatively, an interlock may be provided to prevent
piercing of the receptacle 342 by the transjector assembly 306
until the valve assembly 400 is closed.
[0134] Referring to FIGS. 22 and 25, translation of the handle 338
relative to the housing 302 will be described in greater detail.
The handle assembly 336 further includes a linkage 430 that is
pivotally connected to the housing 302 by pin 432. Connecting the
handle 338 to linkage 392 and linkage 408 is a linkage 434.
Together, linkages 392, 408, 430 and 434 provide a four-bar linkage
system which allow the handle 338 to be moved radially outward from
the housing 302 with the handle 338 being maintained generally
parallel to the housing 302. Further, when the valve assembly 400
is closed and the handle 338 is translated back toward the housing
302, a substantially uniform force is required over the handle's
range of motion. In this way, as the user forces the handle 338
back toward housing 302 to compress the air in the cylinder 390,
the user feels a generally equal resistive force during the entire
compression step. Moreover, the maximum distance that the handle
338 is translated away from the housing 302 is reduced, thereby
making it easier for smaller hand sizes to operate.
[0135] As best shown in FIGS. 22 and 23, the apparatus 300 further
includes a carriage assembly 436 for translating the receptacle 342
within the aperture 340 so that the penetrating element 370 and the
penetrating structures 372 may pierce the lid 376 of the receptacle
342. The carriage assembly 436 includes a thumb toggle 438 that is
pivotally connected to the frame of the housing 302 by a pin 440.
The receptacle 342 is held within a carrier 442 which in turn is
connected to the thumb toggle 438 by a linkage 444. Operation of
the carriage assembly 436 is as follows. Initially, the receptacle
342 is inserted into the aperture 340 as previously described with
the receptacle 342 resting on the carrier 442. The thumb toggle 438
is then depressed to pivot the toggle 438 about pin 440 and to lift
the carrier 442 toward the transjector assembly 306. As best shown
in FIG. 25, the thumb toggle 438 is depressed until the transjector
assembly 306 pierces the lid on the receptacle 342 and the linkage
444 moves over center. When the linkage 444 is over center, the
receptacle 342 is locked in place against the end gasket 368 of the
transjector assembly 306 (see FIG. 25). Preferably, the carriage
assembly 436 will be configured to compensate for overtravel of the
carrier 442. In this way, the carrier 442 will be relaxed after the
receptacle 342 has been pierced by the transjector assembly 306 but
will still provide a sufficient seal between the transjector
assembly 306 and the receptacle 342. To lower the carrier 442, the
thumb toggle 438 is lifted to move the linkage 444 from over
center. The receptacle 342 may then be removed from the aperture
340 by grasping the tab 380 and pulling the receptacle 342 from the
aperture 340.
[0136] Referring to FIGS. 27-29, construction of the release valve
assembly 400 will be described in greater detail. The valve
assembly 400 includes a casing 446 having an inlet port 448 and an
outlet port 450. The outlet tube 398 which connects the cylinder
390 to the valve assembly 400 passes through the inlet port 448.
The interface seal 402 is placed between the outlet port 450 and
the transjector assembly 306 as previously described.
[0137] The valve assembly 400 is shown in the open state in FIG.
28. When open, the poppet 406 is spaced apart from an O-ring seat
452. The poppet 406 is held within a central chamber 454 which is
sealed from the outside environment (except for the outlet port
450) by a diaphragm 456. When open, air introduced into the central
chamber 454 from the outlet tube 398 freely passes around the
poppet 406 and exits the outlet port 450. When closed (see FIG.
29), air introduced into the central chamber 454 from the outlet
tube 398 forces the poppet 406 against the seat 452 which prevents
escape of the compressed air from the central chamber 454. The
valve assembly 400 is preferably configured so that the seal
between the poppet 406 and the seat 452 will hold up to about 120
psi of pressure, and more preferably at about 80 psi.
[0138] To open the valve assembly 400, the release button 418 is
depressed to move the cam 416 from over center and to allow the
poppet 406 to be moved away from the seat 452. To force the poppet
406 away from the seat 452, a spring 457 is provided. The spring
457 will preferably be selected to provide a force sufficient to
overcome the force on the opposite side of the poppet that is
produced by the compressed air within the chamber 454. Hence, when
the release button 418 is depressed, the spring 457 will overcome
the force produced by the compressed air within the chamber 454 and
will promptly force the poppet 406 away from the seat 452 and allow
the valve to open. The valve will rapidly open to allow the
compressed air in the cylinder 390 and tube 398 to almost
instantaneously rush out the central chamber 454 through the outlet
port 450 where it is delivered to the transjector assembly 306 as
previously described. In this manner, the valve assembly 400
operates in a "snap" acting manner to provide a precise amount of
gas to the transjector assembly 306 in a rapid, abrupt and
irreversible manner so that the powder may be sufficiently
aerosolized in a repeatable and a predictable manner.
[0139] Optionally, the housing 302 may further include an
electronic memory chip along with a speaker for providing audible
instructions to a user regarding operation of the apparatus 300.
The chip will preferably be an EPROM, PROM, or PAL chip having
stored electronic information regarding operation of the apparatus
300 and will be configured to be actuated upon deployment of the
capture chamber 304. In this way, as a user prepares for a
treatment, audible instructions will be given. Preferable
instructions include deployment of the chamber 304, charging of the
apparatus with the handle assembly 336, breathing instructions, and
the like, as well as other pertinent information as determined by
the manufacturer.
[0140] Although the foregoing invention has been described in some
detail by way of illustration and example, for purposes of clarity
of understanding, it will be obvious that certain changes and
modifications may be practiced within the scope of the appended
claims.
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