U.S. patent application number 16/170607 was filed with the patent office on 2019-02-28 for aerosolization apparatus with removable mouthpiece.
This patent application is currently assigned to BGP PRODUCTS OPERATIONS GmbH. The applicant listed for this patent is BGP Products Operations GmbH. Invention is credited to John D. Burr, Niccolai Fabrizio, John A. Howard, Adrian E. Smith, Jeff R. Wood.
Application Number | 20190060588 16/170607 |
Document ID | / |
Family ID | 23315559 |
Filed Date | 2019-02-28 |
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United States Patent
Application |
20190060588 |
Kind Code |
A1 |
Burr; John D. ; et
al. |
February 28, 2019 |
Aerosolization apparatus with removable mouthpiece
Abstract
An aerosolization apparatus comprises a body having an inlet, an
endpiece having an outlet, the endpiece being connectable to the
body to define a chamber, wherein the chamber is sized to receive a
capsule containing a pharmaceutical formulation in a manner which
allows the capsule to move within the chamber. The apparatus
further includes a connection mechanism to provide selective
connection of the endpiece to the body, wherein a rotational force
between the endpiece and the body is needed to connect or
disconnect the endpiece from the body, the rotational force being
applied about an axis passing through the chamber. When a user
inhales, air enters into the chamber through the inlet so that the
pharmaceutical formulation is aerosolized within the chamber and
the aerosolized pharmaceutical formulation is delivered to the user
through the outlet. The connection mechanism prevents inadvertent
disconnection of the endpiece from the body.
Inventors: |
Burr; John D.; (Redwood
City, CA) ; Wood; Jeff R.; (Mountain View, CA)
; Smith; Adrian E.; (Belmont, CA) ; Howard; John
A.; (Palo Alto, CA) ; Fabrizio; Niccolai;
(Milan, IT) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
BGP Products Operations GmbH |
Allschwill |
|
CH |
|
|
Assignee: |
BGP PRODUCTS OPERATIONS
GmbH
Allschwill
CH
|
Family ID: |
23315559 |
Appl. No.: |
16/170607 |
Filed: |
October 25, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10298177 |
Nov 14, 2002 |
10124128 |
|
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16170607 |
|
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60336320 |
Nov 14, 2001 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M 2210/0625 20130101;
A61M 15/08 20130101; A61M 15/003 20140204; A61M 2210/0618 20130101;
A61M 2202/206 20130101; A61M 2202/064 20130101; A61M 15/0028
20130101 |
International
Class: |
A61M 15/00 20060101
A61M015/00; A61M 15/08 20060101 A61M015/08 |
Claims
1-35. (canceled)
36. An aerosolization apparatus comprising: a body having an inlet;
an endpiece having an outlet, the endpiece being connectable to the
body to define a chamber, wherein the chamber is sized to receive a
capsule containing a pharmaceutical formulation in a manner which
allows the capsule to move within the chamber; a connector to
provide connection of the endpiece to the body, wherein a
rotational force between the endpiece and the body is needed to
connect and to disconnect the endpiece from the body, the
rotational force being applied about an axis passing through the
chamber; a cap insertable over the endpiece such that a user is
prevented from applying a rotational force between the endpiece and
the body when the cap is inserted over the endpiece; and a
puncturing mechanism capable of providing an opening in the
capsule; whereby when a user inhales, air enters the chamber
through the inlet so that the pharmaceutical formulation is
aerosolized within the chamber and the aerosolized pharmaceutical
formulation is delivered to the user through the outlet.
37. The aerosolization apparatus of claim 36, wherein the connector
comprises engageable threads.
38. The aerosolization apparatus of claim 37, wherein the
engageable threads extend for fewer than two complete turns around
the body.
39. The aerosolization apparatus of claim 37, wherein the
engageable threads have a thread angle of less than about 9
degrees.
40. The aerosolization apparatus of claim 37, wherein the
engageable threads include a recessed portion.
41. The aerosolization apparatus of claim 40, wherein the recessed
portion is recessed at an angle of less than about 75 degrees.
42. The aerosolization apparatus according to claim 36 wherein the
inlet is shaped to provide a swirling air flow in the chamber.
43. The aerosolization apparatus according to claim 36 wherein the
body has a plurality of inlets.
44. The aerosolization apparatus according to claim 36 wherein the
puncturing mechanism is adapted to puncture a single end of the
capsule.
45. The aerosolization apparatus according to claim 36 wherein the
chamber is elongated and has a longitudinal axis, and wherein the
longitudinal axis of the chamber and the longitudinal axis of the
capsule form an angle of less than about 45 degrees during use.
46. The aerosolization apparatus according to claim 36 wherein the
chamber is elongated, wherein the capsule is received lengthwise
within the elongated chamber, and wherein the width of the chamber
is less than the length of the capsule.
47. The aerosolization apparatus of claim 36, wherein the connector
comprises a protrusion that is receivable within a slot, the slot
comprising a longitudinally extending portion and a transversely
extending portion.
48. The aerosolization apparatus according to claim 47 wherein the
slot comprises means for securing the protrusion within the
slot.
49. The aerosolization apparatus according to claim 47 wherein the
slot comprises a bump on the transversely extending portion
configured to secure the protrusion within the slot.
50. The aerosolization apparatus according to claim 47 wherein the
slot comprises one or more sloping surfaces configured to secure
the protrusion within the slot.
51. The aerosolization apparatus according to claim 47 wherein the
slot comprises a second longitudinally extending portion.
52. A method of administering a pharmaceutical formulation to a
patient, the method comprising: inserting a capsule containing a
pharmaceutical formulation into a chamber in a body of an
aerosolization apparatus, the body comprising an inlet, the chamber
being sized to receive a capsule containing a pharmaceutical
formulation in a manner which allows the capsule to move within the
chamber; connecting an endpiece having an outlet to the body by a
connector configured to provide connection of the endpiece to the
body, wherein a rotational force between the endpiece and the body
is needed to connect and to disconnect the endpiece from the body,
the rotational force being applied about an axis passing through
the chamber; puncturing the capsule; administering the
pharmaceutical formulation to the patient by inhalation such that
when the patient inhales through the outlet, air enters the chamber
through the inlet such that the pharmaceutical formulation is
aerosolized within the chamber and the aerosolized pharmaceutical
formulation is delivered to the user through the outlet; and
connecting a cap about the body such that the cap is inserted over
the endpiece to cover at least a portion of the inlet and a user is
prevented from applying a rotational force between the endpiece and
the body when the cap is inserted over the endpiece.
53. The method of claim 52, further comprising, after administering
the pharmaceutical formulation to the patient and prior to
connecting the cap about the body, disconnecting the endpiece from
the body, removing the punctured capsule from the chamber, and
reconnecting the endpiece to the body.
54. A method of administering a pharmaceutical formulation to a
patient, the method comprising: providing a body having an inlet;
providing an endpiece having an outlet, the endpiece being
connectable to the body to define a chamber, wherein the chamber is
sized to receive a capsule containing a pharmaceutical formulation
in a manner which allows the capsule to move within the chamber;
providing a connector to provide connection of the endpiece to the
body, wherein a rotational force between the endpiece and the body
is needed to connect and to disconnect the endpiece from the body,
the rotational force being applied about an axis passing through
the chamber; providing a cap insertable over the endpiece such that
a user is prevented from applying a rotational force between the
endpiece and the body when the cap is inserted over the endpiece;
and providing a puncturing mechanism capable of providing an
opening in the capsule; removing the cap to expose the endpiece;
disconnecting the endpiece from the body by the connector;
inserting the capsule into the chamber; reconnecting the endpiece
to the body by the connector; puncturing the capsule; and
administering the pharmaceutical formulation to the patient by
inhalation such that when the patient inhales through the outlet,
air enters the chamber through the inlet such that the
pharmaceutical formulation is aerosolized within the chamber and
the aerosolized pharmaceutical formulation is delivered to the
patient through the outlet.
55. The method of claim 54, further comprising, after administering
the pharmaceutical formulation to the patient, disconnecting the
endpiece from the body, removing the punctured capsule from the
chamber, reconnecting the endpiece to the body, and inserting the
cap over the endpiece.
Description
RELATED APPLICATIONS
[0001] The present application claims the benefit of U.S.
Provisional Application No. 60/336,320 filed on Nov. 14, 2001.
BACKGROUND
[0002] The need for effective therapeutic treatment of patients has
resulted in the development of a variety of pharmaceutical
formulation delivery techniques. One traditional technique involves
the oral delivery of a pharmaceutical formulation in the form of a
pill, capsule, elixir, or the like. However, oral delivery can in
some cases be undesirable. For example, many pharmaceutical
formulations may be degraded in the digestive tract before they can
be effectively absorbed by the body. Inhaleable drug delivery,
where an aerosolized pharmaceutical formulation is orally or
nasally inhaled by a patient to deliver the formulation to the
patient's respiratory tract, has proven to be a particularly
effective and/or desirable alternative. For example, in one
inhalation technique, a pharmaceutical formulation is delivered
deep within a patient's lungs where it may be absorbed into the
blood stream. Many types of inhalation devices exist including
devices that aerosolize a dry powder, devices comprising a
pharmaceutical formulation stored in or with an inhaleable
propellant, devices which use a compressed gas to aerosolize a
liquid pharmaceutical formulation, and similar devices.
[0003] In one dry powder aerosolization technique, a capsule
containing an inhaleable dry powder is loaded into a chamber in an
aerosolization device. Within the chamber, the dry powder is at
least partially emptied and dispersed to aerosolize the dry powder
so that it may be inhaled by a patient. However, in conventional
devices, the manner of accessing the chamber may often lead to
device inconsistencies and/or failures. Also, the dry powder in the
cavity can cause the access mechanism to become less effective at
efficiently opening and closing.
[0004] Therefore, it is desirable to improve the manner of
accessing an aerosolization device chamber. It is further desirable
to access the chamber in a manner that reduces device
inconsistencies and/or failures. It is still further desirable to
access the cavity so that debris in the cavity will have reduced
adverse affects on the functioning of the device.
SUMMARY
[0005] The present invention satisfies these needs. In one aspect
of the invention an aerosolization apparatus comprises a body and
an endpiece, the body and endpiece being connectable to one another
by a connection mechanism that prevents inadvertent disconnection
of the parts.
[0006] In another aspect of the invention, an aerosolization
apparatus comprises a body having an inlet, an endpiece having an
outlet, the endpiece being connectable to the body to define a
chamber, wherein the chamber is sized to receive a capsule
containing a pharmaceutical formulation in a manner which allows
the capsule to move within the chamber, a connection mechanism to
provide selective connection of the endpiece to the body, wherein a
rotational force between the endpiece and the body is needed to
connect or disconnect the endpiece from the body, the rotational
force being applied about an axis passing through the chamber, and
a puncturing mechanism capable of providing an opening in the
capsule, whereby when a user inhales, air enters into the chamber
through the inlet so that the pharmaceutical formulation is
aerosolized within the chamber and the aerosolized pharmaceutical
formulation is delivered to the user through the outlet.
[0007] In another aspect of the invention, an aerosolization
apparatus comprises a body having an inlet, an endpiece having an
outlet, the endpiece being connectable to the body to define a
chamber, wherein the chamber is sized to receive a capsule
containing a pharmaceutical formulation in a manner which allows
the capsule to move within the chamber, a connection mechanism to
provide selective connection of the endpiece to the body, wherein
the connection mechanism comprises engageable threads, and a
puncturing mechanism capable of providing an opening in the
capsule, whereby when a user inhales, air enters into the chamber
through the inlet so that the pharmaceutical formulation is
aerosolized within the chamber and the aerosolized pharmaceutical
formulation is delivered to the user through the outlet.
[0008] In another aspect of the invention, an aerosolization
apparatus comprises a body having an inlet, an endpiece having an
outlet, the endpiece being connectable to the body to define a
chamber, wherein the chamber is sized to receive a capsule
containing a pharmaceutical formulation in a manner which allows
the capsule to move within the chamber, a connection mechanism to
provide selective connection of the endpiece to the body, wherein
the connection mechanism comprises a protrusion that is receivable
within a slot, the slot comprising a longitudinally extending
portion and a transversely extending portion, and a puncturing
mechanism capable of providing an opening in the capsule, whereby
during inhalation air enters into the chamber through the inlet so
that the pharmaceutical formulation is aerosolized within the
chamber and the aerosolized pharmaceutical formulation is delivered
to the user through the outlet.
[0009] In another aspect of the invention, a method of providing an
aerosolized pharmaceutical formulation comprises providing a body
and an endpiece, the endpiece being connectable to the body when a
rotational force is applied thereto to define a chamber, the
chamber being sized to receive a capsule containing a
pharmaceutical formulation, wherein the rotation force is applied
about an axis that passes through the chamber, and aerosolizing the
pharmaceutical formulation when a user inhales by causing air to
flow through an inlet in the body, within the chamber, and through
an outlet in the endpiece to provide the aerosolized pharmaceutical
formulation to the user.
[0010] In another aspect of the invention, a method of aerosolizing
a pharmaceutical formulation comprises inserting a capsule
containing a pharmaceutical formulation into a chamber in a body,
rotating an endpiece relative to the body to connect the endpiece
to the body, the rotation being about an axis passing through the
chamber, before, during, or after inserting the capsule into the
chamber, providing an opening in the capsule, and inhaling through
an opening in the endpiece to cause air to flow into the chamber
through an inlet in the body thereby aerosolizing the
pharmaceutical formulation.
DRAWINGS
[0011] These features, aspects, and advantages of the present
invention will become better understood with regard to the
following description, appended claims, and accompanying drawings
which illustrate exemplary features of the invention. However, it
is to be understood that each of the features can be used in the
invention in general, not merely in the context of the particular
drawings, and the invention includes any combination of these
features, where:
[0012] FIG. 1 is a schematic sectional side view of a version of an
aerosolization device of the invention with an endpiece and body
connected;
[0013] FIG. 2 is a schematic sectional side view of the version of
an aerosolization device of FIG. 1 with the endpiece and body
disconnected;
[0014] FIG. 3 is a schematic sectional side view of a version of an
aerosolization device in use;
[0015] FIG. 4A is a schematic sectional side view of another
version of an aerosolization device;
[0016] FIG. 4B is a schematic prospective view of the
aerosolization device of FIG. 4A;
[0017] FIG. 4C is a schematic section view along section A-A in
FIG. 4B;
[0018] FIGS. 5A through 5C are schematic views of versions of
connection mechanisms for use with an aerosolization device;
[0019] FIG. 6A is a schematic sectional side view of a portion of
another version of an aerosolization device;
[0020] FIG. 6B is a schematic end view of the body of the version
of an aerosolization device of FIG. 6A;
[0021] FIG. 6C is a schematic sectional side view of the version of
the aerosolization device of FIG. 6A in a connected
configuration;
[0022] FIGS. 7A and 7B are schematic sectional and schematic
perspective views, respectively, of a portion of another version of
an aerosolization device;
[0023] FIG. 8 is a schematic perspective view of a portion of
another version of an aerosolization device;
[0024] FIG. 9 is a schematic side view of a body of a version of an
aerosolization device;
[0025] FIG. 10 is a schematic sectional side view of a body of
another version of an aerosolization device; and
[0026] FIGS. 11A though 11M illustrate parts of a specific version
of an aerosolization device.
DESCRIPTION
[0027] The present invention relates to delivering an aerosolized
pharmaceutical formulation to a patient. Although the process is
illustrated in the context of aerosolizing a dry powder
pharmaceutical formulation, the present invention can be used in
other processes and should not be limited to the examples provided
herein.
[0028] An aerosolization device 100 of the present invention is
shown schematically in FIG. 1. The aerosolization device 100
includes a body 105 and an endpiece 110 that may be attached to the
body 105 to form a chamber 115 within the interior of the body 105
and the endpiece 110. The endpiece 110 includes an end 120 defining
an outlet 125. The end 120 may be sized and shaped to be received
in a user's mouth. Alternatively, the end 120 may be sized and
shaped to be received in a nostril of a user or may sized and
shaped to be received by a mask, a spacer chamber, a respirator
circuit, or the like. The body includes one or more inlets 130 in
communication with the chamber 115. Together the inlets 130, the
chamber 115, and the outlet 125 define an airway through the
aerosolization device 100. Accordingly, when a user contacts the
endpiece 110 and inhales or otherwise creates a vacuum at the
outlet 125, a pharmaceutical formulation with the chamber 115 may
be delivered to the user through the outlet 125. In one version,
the pharmaceutical formulation may be contained within a capsule
that is positionable within the chamber 115, the chamber 115 being
sized to receive the capsule in a manner which allows the capsule
to move within the chamber 115. In this version, the endpiece 110
includes a perforated member 135 having one or more openings 140
therein. The perforated member 135 sufficiently blocks the chamber
115 to retain a capsule in the chamber 115, while the openings 140
allow air and/or other material to pass to the outlet 125. A
connection mechanism 150 may be provided to allow the endpiece 110
to be attached to the body 105.
[0029] In one version, as shown in FIG. 2, the connection mechanism
150 may allow the body 105 and the endpiece 110 to be disconnected
to allow for access to the chamber 115. In this version, the
endpiece 110 may be disconnected from the body 105 to allow a
pharmaceutical formulation to be inserted into the chamber, for
example by allowing a capsule to be inserted into the chamber 115.
In this version, the connection mechanism includes a body
connection member 150a that cooperates with an endpiece connection
member 150b to selectively connect and disconnect the endpiece 110
to the body 105.
[0030] After a capsule 160 has been inserted into the chamber 115,
the endpiece 110 may again be attached to the body 105 to secure
the capsule 160 within the chamber 115, as shown in FIG. 3. The
capsule 160 is opened, for example by puncturing the capsule 160
prior to insertion or within the chamber 115, such as by
longitudinally advancing a sliding puncture mechanism 162. When
opened, the pharmaceutical formulation in the capsule is allowed to
exit the capsule 160. In one version, the pharmaceutical
formulation is in a dry powder form and the flow of air through the
airway causes the pharmaceutical formulation to be aerosolized. For
example, as shown in FIG. 3, a user may contact the endpiece 110
with his or her mouth and inhale, thereby drawing air through the
outlet 125, as shown by arrow 165. This inhalation causes air to be
taken in through the inlets 130, as shown by arrows 170. The air
taken in causes the capsule 160 to agitate within the chamber 115.
The agitation causes the dry powder pharmaceutical formulation to
leave the capsule 160 and become aerosolized in the airway. The
aerosolized pharmaceutical formulation passes through the
perforated member 135 and is delivered to the user where it may be
inhaled to a position in the user's respiratory tract. In one
particular embodiment, a plurality of inlets 130 may be designed to
cause the inlet air 170 to swirl within the chamber, for example,
by being at least partially tangentially oriented as described in
U.S. Pat. 4,995,385 and U.S. Pat. 4,069,819, both of which are
incorporated herein by reference in their entireties. In such an
arrangement, the chamber 115 comprises a longitudinal axis that
lies generally in the inhalation direction 165, and the capsule 160
is insertable lengthwise into the chamber 115 so that the capsule's
longitudinal axis may be parallel to the longitudinal axis of the
chamber 115. The swirling air flow then causes the capsule to
rotate within the chamber 115 in a manner where the longitudinal
axis of the capsule is remains at an angle less than 80 degrees,
and preferably less than 45 degrees from the longitudinal axis of
the chamber. In one version, this rotation is caused by the width
of the chamber being less than the length of the capsule.
[0031] Often, a user will grasp the body 105 during use while
inhaling through the endpiece 110. It has been discovered that
doing so may create a disconnection force in the inhalation
direction 165 between the body 105 and the endpiece 110.
Accordingly, the connection mechanism 150 may be designed to
prevent undesired disconnection of the endpiece 110 from the body
105 during use.
[0032] In one version, the connection mechanism 150 requires a
force to be applied at least partially in a direction other than in
an inhalation direction 165 in order to disconnect the endpiece 110
from the body 105. Thus, in this version, the user's inadvertent
forcing apart of the endpiece 110 and the body 105 during use does
not generate a force in the direction required for disconnection.
For example, the force required for disconnection may be a
rotational force. In one particularly preferred version, the
rotational force is a rotational force applied about an axis that
passes through the chamber. For example, the rotational force may
be applied about an axis that passes through the chamber and is
parallel or coaxial with a longitudinal axis passing through the
chamber. Such a rotational force is generally not generated by a
user during inhalation making inadvertent disconnection more
difficult. Examples of connection mechanisms of this type are
schematically shown in FIGS. 4-10.
[0033] In the version of FIGS. 4A, 4B, and 4C the aerosolization
device 100 comprises a connection mechanism 150 including a
protrusion 175 on the endpiece 110 and a groove or slot 180 on the
body 105. Alternatively, the protrusion 175 may be provided on the
body 105 and the slot 180 may be provided on the endpiece 110. The
protrusion 175 is insertable into the slot 180 for attachment of
the endpiece 110 to the body 105. For example, in the version
shown, the slot 180 may comprise a longitudinally extending portion
185 and a transversely extending portion 190. To connect the parts,
the protrusion 175 is inserted into the longitudinally extending
portion 185 until it is in a position in alignment with the
transversely extending portion 190 at which time the endpiece 110
is twisted relative to the body 105 to cause the protrusion 175 to
slide within the transversely extending portion 190. When the
protrusion 175 is within the transversely extending portion 190,
the walls of the transversely extending portion 190 prevent
movement of the protrusion 175, and thus movement of the endpiece
110 in the inhalation direction 165. Accordingly, when the user
inhales on the endpiece 110, the endpiece 110 is prevented from
disconnecting with the body 105 as a result of forces in the
inhalation direction 165 alone. FIG. 4C is a cross-section along
line A-A of the transversely extending portion 190. As shown, the
transversely extending portion 190 extends partly around the
circumference of the body 105. Alternatively, the transversely
extending portion 190 may extend completely around the body 105 or
to a different circumferential position than the position
shown.
[0034] The slot 180 may further be designed to help secure the
protrusion 175 within the slot 180. For example, as shown in FIGS.
5A, 5B, and 5C, the transversely extending portion 190 may include
a member which serves to secure the protrusion 175 within the
transversely extending portion 190. In the version of FIG. 5A, a
projection 195 such as a bump is provided on the base of the
transversely extending portion 190. When sufficient rotational
force is applied, the protrusion 175 may slide over the projection
195 to be positioned in a secured position 200 in the slot 180,
thereby providing a snap fit. To disconnect the parts, the endpiece
110 may be twisted in the opposite direction with sufficient force
to cause the protrusion 175 to again slide past the projection 195.
Additionally or alternatively, one or More projections 195 may be
provided on the side walls of the transversely extending portion
190. In the version of FIG. 5B, the depth of the base 205 of the
transversely extending portion 190 gradually lessens. Accordingly,
as the protrusion 175 is slid in the transversely extending portion
190, the frictional forces increase and the protrusion 175 may be
wedged into a secure position within the slot 180. To disconnect
this version, a sufficient force is applied to overcome the wedging
of the protrusion 175 in the transversely extending portion 190.
Alternatively, the side walls of the transversely extending portion
may be somewhat V-shaped to create the wedging effect. In the
version shown in FIG. 5C, the slot 180 comprises a second
longitudinally extending portion 207 spaced from the longitudinally
extending portion 185 and communicable therewith by the
transversely extending portion 190. When in the forward region of
the second longitudinally extending portion 207, the protrusion 175
is prevented from movement in the transverse direction and from
movement in the inhalation direction 165. Thus, force generated
during inhalation does not cause disconnection. To disconnect, the
endpiece is moved in a direction opposite to the inhalation
direction 165. A projection or a wedging surface, as discussed
above, may be further provided in the second longitudinally
extending portion 207 to further secure the protrusion 175.
Optionally, a biasing member, such as a compressed spring, may be
positioned to bias the protrusion in the inhalation direction 165
when the protrusion is in the slot 180. The biasing member will
serve to secure the protrusion in the second longitudinally
extending portion 207 until the user applies a force sufficient to
overcome the bias.
[0035] In another version, as shown for example in FIGS. 6A, 6B,
and 6C, the aerosolization device 100 comprises a connection
mechanism 150 with a longitudinally extending protrusion 210 that
is receivable in an interior slot 215. In the version shown, the
longitudinal protrusion 210 is provided on the endpiece 110 and the
interior slot 215 is provided on the body 105. Alternatively, this
may be reversed. The interior slot 215 includes a collar 220 which
is receivable in a recess 225 on the protrusion 210 to prevent
movement of the endpiece 110 in the inhalation direction 165 when
the endpiece 110 is attached to the body 105, as shown in the
connected configuration shown in FIG. 6C. A portion of the collar
220 is reduced in size or thinned to provide a longitudinal access
230 to the slot 215, as best shown in FIG. 6B which is an end view
of the body 105 along line B-B. To attach the endpiece 110 to the
body 105 in this version, the protrusion 210 is inserted into the
longitudinal access 230 of the slot 215 until the end portion 235
extends beyond the collar 220. The endpiece 110 is then twisted so
that the end portion 235 is positioned behind the collar 220 and
prevented from moving in the inhalation direction 165. A snap fit
projection or a sloped wedging surface, as discussed above, may be
provided in the slot 215 to further secure the protrusion 210
within the slot 215. Optionally, multiple protrusions and slots may
be provided, as shown.
[0036] As can be seen in FIG. 6C, this version of the
aerosolization device 100 also provides a substantially smooth
surface 240 within the chamber 115. This smooth surface 240 may be
advantageous in increasing the aerosolization space in the chamber
115 thereby creating more space in which a capsule may rattle.
Additionally, the less discontinuous surface may provide more
consistent rattling of the capsule and, thus, more consistent
emptying of the capsule. FIGS. 7A and 7B show another version of a
connection mechanism 150 that provides a smooth surface when in a
connected configuration. In this version, a longitudinal protrusion
245 extends from the body 105 and is insertable into an opening 250
in the end surface 255 in the endpiece 110. Alternatively, the
protrusion 245 and opening 250 may be reversed. The opening 250
includes a collar 260 that may be engaged around or near a recess
265 on the protrusion 245 when in a connected configuration to
prevent the endpiece 110 from moving relative to the body 105 in
the inhalation direction 165. To connect the parts, an end portion
270 of the protrusion 245 is inserted into the opening 250 at an
enlarged area 280, as best shown in FIG. 7B. The parts are then
rotated relative to one another so that the end portion 270 is
secured within a cavity 275 beyond the collar 260. The cavity 275
may have snap fit projections or wedging surfaces, as discussed
above, to further secure the protrusion 245 within the opening 250.
Multiple protrusions 245 and openings 250 may be provided.
[0037] In the versions of FIGS. 4 through 7, indicia may be
provided to aid the user when connecting or disconnecting the
endpiece 110 to the body 105. For example, as shown in the version
of FIG. 7B, a first marking 285 may be provided on the outer
surface of the endpiece 110 and a second marking 290 may be
provided on the outer surface of the body 105. When the first
marking 285 and the second marking 290 are aligned with one
another, the two parts may be disconnected. Additionally or
alternatively, markings may be provided to indicate to the user in
which direction to twist the parts in order to connect or to
disconnect the parts.
[0038] Another version of an aerosolization device 100 comprising a
connection mechanism 150 that must at least partially be forced in
a direction other than an inhalation direction 165 is shown in FIG.
8. In this version, the body 105 includes a male portion 300 that
is insertable into a female portion 305 on the endpiece 110. On the
male portion 300 are external threads 310 that may engage internal
threads 315 on the endpiece 110. Accordingly, the endpiece 110 may
be attached to the body 105 by screwing the parts together. The
threaded engagement prevents the endpiece 110 from disconnecting
from the body 105 when a force in the inhalation direction 165 is
applied. It has been discovered that this arrangement prevents
disconnection of the parts during inhalation by a user.
Alternatively, the threaded arrangement shown in FIG. 8 may be
switched so that the male portion 300 is on the endpiece 110 and
the female portion 305 is on the body 105. The threads may be
standard helical threads. Alternatively, the threads may comprise a
series of bumps and/or posts that mate in a screw-like manner.
[0039] The thread arrangement may be designed to further prevent
disconnection of the endpiece 110 from the body 105 during use. For
example, FIG. 9 shows a version of a threaded portion having
threads of high pitch. It has been determined that when the thread
angle, a, is less than about 9 degrees, inhalation forces in the
inhalation direction 165 are not sufficient to unscrew the parts.
Accordingly, in one version, the threads have a thread angle of
less than about 9 degrees, and more preferably less than about 7
degrees. Alternatively or additionally, the threads may be shaped
to further prevent disconnection of the endpiece 110 and the body
105 when a force in the inhalation direction 165 is applied. For
example, in the version shown in FIG. 10, the threads have a
recessed backside 320 to provide interlocking of the threads and
thereby preventing stripping of the threads when stressed. In one
version, the recess angle, b, is less than 90 degrees, more
preferably less than about 75 degrees, and most preferably less
than about 60 degrees. The mating threads on the opposing part are
shaped to be received in the recessed backside 320.
[0040] FIGS. 11A though 11M illustrate parts from a specific
version of an aerosolization device 100. FIGS. 11A and 11B show,
respectively, a sectional view and a side view of a cap 500 that
may be inserted over an endpiece 110. FIGS. 11C and 11D show,
respectively, a sectional view and a side view of a specific
version 505 of a body 105. The version includes a plurality of
angled slots 510 that provide an inlet 130 into the chamber 115.
FIGS. 11E and 11F show, respectively, a sectional view and a side
view of a version 515 of an endpiece 110. The endpiece 110 may be
connected and disconnect to the body 105 by rotational force. FIG.
11G shows an end view of the endpiece 110 of FIG. 11E showing an
arcuate version 520 of a perforated member 135 within the endpiece
110. FIGS. 11H and 11I show, respectively, a version 525 of a
puncturing mechanism 162. A U-shaped puncturing member 530, as
shown in FIG. 11J, is seated in the end of a slidable member 535.
As shown in FIG. 11K, a position 540 on the device may be used to
provide a marking on the device. FIGS. 11L and 11K show,
respectively, a sectional view and a side view of an assembled
device according to the version of FIGS. 11A through 11J. To use
the aerosolization device 100 of FIGS. 11A through 11J, a user
takes an assembled device, as shown in Figure 11L, and removes the
cap 500. Then, the user twists the endpiece 515 to cause the
interior threads on the endpiece 515 to be separated from the
exterior threads on the body 505 to disconnect the endpiece 515
from the body 505, thereby providing access to the chamber 115 so
that the user may insert a capsule containing a pharmaceutical
formulation. After insertion, the endpiece 515 is connected to the
body by threaded engagement and the puncturing mechanism 525 is
advanced to create one or more openings into the capsule. The user
then places his or her mouth or nose on the endpiece 515 and
inhales through the endpiece 515. The inhalation causes air to flow
through the inlets 510 and into the chamber 115 where it causes the
capsule to be swirled in a manner which causes the pharmaceutical
formulation to be aerosolized. The aerosolized pharmaceutical
formulation then flows through the endpiece and into the user's
respiratory tract. The twist attachment of the endpiece 515 to the
body 505 prevents the inadvertent disconnection of the endpiece 515
as a result of inhalation pressure and thereby reduces the risk of
inhalation of the endpiece 515.
[0041] In a preferred version, the invention provides a system and
method for aerosolizing a pharmaceutical formulation and delivering
the pharmaceutical formulation to the lungs of the user. The
pharmaceutical formulation may comprise powdered medicaments,
liquid solutions or suspensions, and the like, and may include an
active agent.
[0042] The active agent described herein includes an agent, drug,
compound, composition of matter or mixture thereof which provides
some pharmacologic, often beneficial, effect. This includes foods,
food supplements, nutrients, drugs, vaccines, vitamins, and other
beneficial agents. As used herein, the terms further include any
physiologically or pharmacologically active substance that produces
a localized or systemic effect in a patient. An active agent for
incorporation in the pharmaceutical formulation described herein
may be an inorganic or an organic compound, including, without
limitation, drugs which act on: the peripheral nerves, adrenergic
receptors, cholinergic receptors, the skeletal muscles, the
cardiovascular system, smooth muscles, the blood circulatory
system, synoptic sites, neuroeffector junctional sites, endocrine
and hormone systems, the immunological system, the reproductive
system, the skeletal system, autacoid systems, the alimentary and
excretory systems, the histamine system, and the central nervous
system. Suitable active agents may be selected from, for example,
hypnotics and sedatives, psychic energizers, tranquilizers,
respiratory drugs, anticonvulsants, muscle relaxants, antiparkinson
agents (dopamine antagnonists), analgesics, anti-inflammatories,
antianxiety drugs (anxiolytics), appetite suppressants,
antimigraine agents, muscle contractants, anti-infectives
(antibiotics, antivirals, antifungals, vaccines) antiarthritics,
antimalarials, antiemetics, anepileptics, bronchodilators,
cytokines, growth factors, anti-cancer agents, antithrombotic
agents, antihypertensives, cardiovascular drugs, antiarrhythmics,
antioxicants, anti-asthma agents, hormonal agents including
contraceptives, sympathomimetics, diuretics, lipid regulating
agents, antiandrogenic agents, antiparasitics, anticoagulants,
neoplastics, antineoplastics, hypoglycemics, nutritional agents and
supplements, growth supplements, antienteritis agents, vaccines,
antibodies, diagnostic agents, and contrasting agents. The active
agent, when administered by inhalation, may act locally or
systemically.
[0043] The active agent may fall into one of a number of structural
classes, including but not limited to small molecules, peptides,
polypeptides, proteins, polysaccharides, steroids, proteins capable
of eliciting physiological effects, nucleotides, oligonucleotides,
polynucleotides, fats, electrolytes, and the like.
[0044] Examples of active agents suitable for use in this invention
include but are not limited to one or more of calcitonin,
erythropoietin (EPO), Factor VIII, Factor IX, ceredase, cerezyme,
cyclosporin, granulocyte colony stimulating factor (GCSF),
thrombopoietin (TPG), alpha-1 proteinase inhibitor, elcatonin,
granulocyte macrophage colony stimulating factor (GMCSF), growth
hormone, human growth hormone (HGH), growth hormone releasing
hormone (GHRH), heparin, low molecular weight heparin (LMWH),
interferon alpha, interferon beta, interferon gamma, interleukin-1
receptor, interleukin-2, interleukin-1 receptor antagonist,
interleukin-3, interleukin-4, interleukin-6, luteinizing hormone
releasing hormone (LHRH), factor IX, insulin, pro-insulin, insulin
analogues (e.g., mono-acylated insulin as described in U.S. Pat.
No. 5,922,675, which is incorporated herein by reference in its
entirety), amylin, C-peptide, somatostatin, somatostatin analogs
including octreotide, vasopressin, follicle stimulating hormone
(FSH), insulin-like growth factor (IGF), insulintropin, macrophage
colony stimulating factor (M-CSF), nerve growth factor (NGF),
tissue growth factors, keratinocyte growth factor (KGF), glial
growth factor (GGF), tumor necrosis factor (TNF), endothelial
growth factors, parathyroid hormone (PTH), glucagon-like peptide
thymosin alpha 1, IIb/IIIa inhibitor, alpha-1 antitrypsin,
phosphodiesterase (PDE) compounds, VLA-4 inhibitors,
bisphosponates, respiratory syncytial virus antibody, cystic
fibrosis transmembrane regulator (CFTR) gene, deoxyreibonuclease
(Dnase), bactericidal/permeability increasing protein (BPI),
anti-CMV antibody, 13-cis retinoic acid, macrolides such as
erythromycin, oleandornycin, troleandomycin. roxithromycin,
clarithromycin, davercin, azithromycin, flurithromycin,
dirithromycin, josamycin, spiramycin, midecamycin, leucornycin,
miocamycin, rokitamycin, andazithromycin, and swinolide A;
fluoroquinolones such as ciprofloxacin, ofloxacin, levofloxacin,
trovafloxacin, alatrofloxacin, moxifloxicin, norfloxacin, enoxacin,
grepafloxacin, gatifloxacin, lomefloxacin, sparfloxacin,
temafloxacin, pefloxacin, amifloxacin, fleroxacin, tosufloxacin,
prulifloxacin, irloxacin, pazufloxacin, clinafloxacin, and
sitafloxacin, aminoglycosides such as gentamicin, netilmicin,
paramecin, tobramycin, amikacin, kanamycin, neomycin, and
streptomycin, vancomycin, teicoplanin, rampolanin, mideplanin,
colistin, daptornycin, gramicidin, colistimethate, polymixins such
as polymixin B, capreomycin, bacitracin, penems; penicillins
including penicllinase-sensitive agents like penicillin G,
penicillin V, penicillinase-resistant agents like methicillin,
oxacillin, cloxacillin, dicloxacillin, floxacillin, nafcillin; gram
negative microorganism active agents like ampicillin, amoxicillin,
and hetacillin, cillin, and galampicillin; antipseudomonal
penicillins like carbenicillin, ticarcillin, azlocillin,
mezlocillin, and piperacillin; cephalosporins like cefpodoxime,
cefprozil, ceftbuten, ceftizoxime, ceftriaxone, cephalothin,
cephapirin, cephalexin, cephradrine, cefoxitin, cefamandole,
cefazolin, cephaloridine, cefaclor, cefadroxil, cephaloglycin,
cefuroxime, ceforanide, cefotaxime, cefatrizine, cephacetrile,
cefepime, cefixime, cefonicid, cefoperazone, cefotetan,
cefrnetazole, ceftazidime, loracarbef, and moxalactam, monobactams
like aztreonam; and carbapenems such as imipenem, meropenem,
pentamidine isethionate, albuterol sulfate, lidocaine,
metaproterenol sulfate, beclomethasone diprepionate, triamcinolone
acetamide, budesonide acetonide, fluticasone, ipratropium bromide,
flunisolide, cromolyn sodium, ergotamine tartrate and where
applicable, analogues, agonists, antagonists, inhibitors, and
pharmaceutically acceptable salt forms of the above. In reference
to peptides and proteins, the invention is intended to encompass
synthetic, native, glycosylated, unglycosylated, pegylated forms,
and biologically active fragments and analogs thereof.
[0045] Active agents for use in the invention further include
nucleic acids, as bare nucleic acid molecules, vectors, associated
viral particles, plasmid DNA or RNA or other nucleic acid
constructions of a type suitable for transfection or transformation
of cells, i.e., suitable for gene therapy including antisense.
Further, an active agent may comprise live attenuated or killed
viruses suitable for use as vaccines. Other useful drugs include
those listed within the Physician's Desk Reference (most recent
edition).
[0046] The amount of active agent in the pharmaceutical for
ululation will be that amount necessary to deliver a
therapeutically effective amount of the active agent per unit dose
to achieve the desired result. In practice, this will vary widely
depending upon the particular agent, its activity, the severity of
the condition to he treated, the patient population, dosing
requirements, and the desired therapeutic effect. The composition
will generally contain anywhere from about 1% by weight to about
99% by weight active agent, typically from about 2% to about 95% by
weight active agent, and more typically from about 5% to 85% by
weight active agent, and will also depend upon the relative amounts
of additives contained in the composition. The compositions of the
invention are particularly useful for active agents that are
delivered in doses of from 0.001 mg/day to 100 mg/day, preferably
in doses from 0.01 mg/day to 75 mg/day, and more preferably in
doses from 0.10 giday to 50 mg/day. It is to be understood that
more than one active agent may be incorporated into the
formulations described herein and that the use of the term "agent"
in no way excludes the use of two or more such agents.
[0047] The pharmaceutical formulation may comprise a
pharmaceutically acceptable excipient or carrier which may be taken
into the lungs with no significant adverse toxicological effects to
the subject, and particularly to the lungs of the subject. In
addition to the active agent, a pharmaceutical formulation may
optionally include one or more pharmaceutical excipients which are
suitable for pulmonary administration. These excipients, if
present, are generally present in the composition in amounts
ranging from about 0.01% to about 95% percent by weight, preferably
from about 0.5 to about 80%, and more preferably from about 1 to
about 60% by weight. Preferably, such excipients will, in part,
serve to further improve the features of the active agent
composition, for example by providing more efficient and
reproducible delivery of the active agent, improving the handling
characteristics of powders, such as flowability and consistency,
and/or facilitating manufacturing and filling of unit dosage forms.
In particular, excipient materials can often function to further
improve the physical and chemical stability of the active agent,
minimize the residual moisture content and hinder moisture uptake,
and to enhance particle size, degree of aggregation, particle
surface properties, such as rugosity, ease of inhalation, and the
targeting of particles to the lung. One or more excipients may also
be provided to serve as bulking agents when it is desired to reduce
the concentration of active agent in the formulation.
[0048] Pharmaceutical excipients and additives useful in the
present pharmaceutical formulation include but are not limited to
amino acids, peptides, proteins, non-biological polymers,
biological polymers, carbohydrates, such as sugars, derivatized
sugars such as alditols, aldonic acids, esterified sugars, and
sugar polymers, which may be present singly or in combination.
Suitable excipients are those provided in WO 96/32096, which is
incorporated herein by reference in its entirety. The excipient may
have a glass transition temperatures (Tg) above about 35.degree.
C., preferably above about 40.degree. C., more preferably above
45.degree. C., most preferably above about 55.degree. C.
[0049] Exemplary protein excipients include albumins such as human
serum albumin (HSA), recombinant human albumin (rHA), gelatin,
casein, hemoglobin, and the like. Suitable amino acids (outside of
the dileucyl-peptides of the invention), which may also function in
a buffering capacity, include alanine, glycine, arginine, betaine,
histidine, glutamic acid, aspartic acid, cysteine, lysine, leucine,
isoleucine, valine, methionine, phenylalanine, aspartame, tyrosine,
tryptophan, and the like. Preferred are amino acids and
polypeptides that function as dispersing agents. Amino acids
falling into this category include hydrophobic amino acids such as
leucine, valine, isoleucine, tryptophan, alanine, methionine,
phenylalanine, tyrosine, histidine, and proline.
Dispersibility-enhancing peptide excipients include dimers,
trimers, tetramers, and pentamers comprising one or more
hydrophobic amino acid components such as those described
above.
[0050] Carbohydrate excipients suitable for use in the invention
include, for example, monosaccharides such as fructose, maltose,
galactose, glucose, D-mannose, sorbose, and the like;
disaccharides, such as lactose, sucrose, trehalose, cellobiose, and
the like; polysaccharides, such as raffinose, melezitose,
maltodextrins, dextrans, starches, and the like; and alditols, such
as mannitol, xylitol, maltitol, lactitol, xylitol sorbitol
(glucitol), pyranosyl sorbitol, myoinositol and the like.
[0051] The pharmaceutical formulation may also include a buffer or
a pH adjusting agent, typically a salt prepared from an organic
acid or base. Representative buffers include organic acid salts of
citric acid, ascorbic acid, gluconic acid, carbonic acid, tartaric
acid, succinic acid, acetic acid, or phthalic acid, Tris,
tromethamine hydrochloride, or phosphate buffers.
[0052] The pharmaceutical formulation may also include polymeric
excipients/additives, e.g., polyvinylpyrrolidones, derivatized
celluloses such as hydroxymethylcellulose, hydroxyethylcellulose,
and hydroxypropylmethylcellulose, Ficolls (a polymeric sugar),
hydroxyethylstarch, dextrates (e.g., cyclodextrins, such as
2-hydroxypropyl-.beta.-cyclodextrin and
sulfobutylether-.beta.-cyclodextrin), polyethylene glycols, and
pectin.
[0053] The pharmaceutical formulation may further include flavoring
agents, taste-masking agents, inorganic salts (for example sodium
chloride), antimicrobial agents (for example benzalkonium
chloride), sweeteners, antioxidants, antistatic agents, surfactants
(for example polysorbates such as "TWEEN 20" and "TWEEN 80"),
sorbitan esters, lipids (for example phospholipids such as lecithin
and other phosphatidylcholines, phosphatidylethanolamines), fatty
acids and fatty esters, steroids (for example cholesterol), and
chelating agents (for example EDTA, zinc and other such suitable
cations). Other pharmaceutical excipients and/or additives suitable
for use in the compositions according to the invention are listed
in "Remington: The Science & Practice of Pharmacy", 19.sup.th
ed., Williams & Williams, (1995), and in the "Physician's Desk
Reference", 52.sup.nd ed., Medical Economics, Montvale, N.J.
(1998), both of which are incorporated herein by reference in their
entireties.
[0054] "Mass median diameter" or "MMD" is a measure of mean
particle size, since the powders of the invention are generally
polydisperse (i.e., consist of a range of particle sizes). MMD
values as reported herein are determined by centrifugal
sedimentation, although any number of commonly employed techniques
can be used for measuring mean particle size. "Mass median
aerodynamic diameter" or "MMAD" is a measure of the aerodynamic
size of a dispersed particle. The aerodynamic diameter is used to
describe an aerosolized powder in terms of its settling behavior,
and is the diameter of a unit density sphere having the same
settling velocity, generally in air, as the particle. The
aerodynamic diameter encompasses particle shape, density and
physical size of a particle. As used herein, MMAD refers to the
midpoint or median of the aerodynamic particle size distribution of
an aerosolized powder determined by cascade impaction.
[0055] In one version, the powdered formulation for use in the
present invention includes a dry powder having a particle size
selected to permit penetration into the alveoli of the lungs, that
is, preferably 10 .mu.m mass median diameter (MMD), preferably less
than 7.5 .mu.m, and most preferably less than 5 .mu.m, and usually
being in the range of 0.1 .mu.m to 5 .mu.m in diameter. The
delivered dose efficiency (DDE) of these powders may be greater
than 30%, more preferably greater than 40%, more preferably greater
than 50% and most preferably greater than 60% and the aerosol
particle size distribution is about 1.0-5.0 .mu.m mass median
aerodynamic diameter (MMAD), usually 1.5-4.5 .mu.m MMAD and
preferably 1.5-4.0 .mu.m MMAD. These dry powders have a moisture
content below about 10% by weight, usually below about 5% by
weight, and preferably below about 3% by weight. Such powders are
described in WO 95/24183, WO 96/32149, WO 99/16419, and WO
99/16422, all of which are all incorporated herein by reference in
their entireties.
[0056] Although the present invention has been described in
considerable detail with regard to certain preferred versions
thereof, other versions are possible, and alterations, permutations
and equivalents of the version shown will become apparent to those
skilled in the art upon a reading of the specification and study of
the drawings. For example, the cooperating components may be
reversed or provided in additional or fewer number. Also, the
various features of the versions herein can be combined in various
ways to provide additional versions of the present invention.
Furthermore, certain terminology has been used for the purposes of
descriptive clarity, and not to limit the present invention.
Therefore, the appended claims should not be limited to the
description of the preferred versions contained herein and should
include all such alterations, permutations, and equivalents as fall
within the true spirit and scope of the present invention.
* * * * *