Patent Application
20100199984
The present invention relates to a nasal drug delivery device for delivery of liquid medicament to the nasal cavity, particularly the nasal epithelia.
Nasal delivery of pharmaceutical products can be useful both for treating diseases or disorders in the nasal passages themselves and for treating systemic and/or neurological disorders. However, it has been observed that particle or droplet size has significant impact on absorption when administering drugs via the nose and the nasal epithelia. Smaller droplets have been shown to impact on the higher nasal turbinates which promotes better absorption into the body. On the other hand, droplets that are too small, and/or are delivered at too high a velocity, can be carried beyond the nasal passageway and undesirably find their way into the pulmonary region. Indeed, FDA Guidelines require testing to demonstrate that only a minimal amount of drug from a nasal delivery device be deposited beyond the nasal passageway and find its way into the pulmonary region.
Delivery of pharmaceutical products via the nasal epithelia offers a drug delivery route that can bypass the “blood brain barrier” in some situations. As such, the nasal epithelia can be a useful route both for delivering pharmaceutical products for treating diseases or disorders in the nasal passages themselves and for delivering pharmaceutical products for treating systemic and/or neurological disorders. However, it has been observed that particle or droplet size has significant impact on absorption when administering drugs via the nose and the nasal epithelia. Smaller droplets have been shown to impact on the higher nasal turbinates which promotes better absorption into the body. On the other hand, droplets that are too small, and/or are delivered at too high a velocity, can be carried beyond the nasal passageway and undesirably find their way into the pulmonary region. Indeed, FDA Guidelines require testing to demonstrate that only a minimal amount of drug from a nasal delivery device be deposited beyond the nasal passageway and find its way into the pulmonary region.
Traditional devices for supplying drugs to the nasal epithelia include syringed nose drops, pump spray devices, and fluorinated propellant metered dose inhalers (MDI). These traditional devices have not generally been able to achieve the particle sizes necessary to maximize efficacy while helping mitigate undesired pulmonary absorption. For example, both eye dropper type devices and simple spray devices typically present medicament into the nasal cavity in a stream. The result is that much of the medicament simply runs out of the patient's nose, and only a small amount of the drug is absorbed, with even less of the drug reaching the nasal epithelia.
Newer pump type devices have increased ability to reduce the particle size of the medicament but have drawbacks of their own. Most pump devices rely on the user's hand strength to overcome a spring pressure in the pump, and create a pumping action. However, many individuals end up with less than optimal sprays produced from such pumps because of the variation in action of applying the necessary power to the pump and/or the variability in hand strength. Other devices, known as metered dose propellant type devices, tend to produce good particle size, but at an undesirably high effective velocity. The pressure of the propellant in these devices tends to cause the drug to escape the nasal passageways and thus be deposited in the lungs or other portions of the pulmonary region.
Further, it has been observed that when a human exhales air from the lungs though the mouth, and particularly in instances where the exhalation is impeded by something that creates a backpressure in the pulmonary system, the soft palate operates to isolate and insulate the nasal pharynx from the remainder of the pulmonary system. That is, the soft palate acts as a natural check valve preventing the flow of air between the lungs and the nasal cavity. Thus, it is believed that nasal drug delivery can be improved if the patient is exhaling orally while the drug is being sprayed into the nasal passages. One nasal delivery system that takes advantage of this is shown in U.S. Patent Application Publication 2006/0289007, which is incorporated herein by reference. The '9007 publication discloses using a pressurized canister of the type typically found in metered dose inhalers, which may not be appropriate for all situations.
Accordingly, there remains a need for alternative means of delivering a desired amount of drug to the nasal epithelia, advantageously in desired particle size distribution, and/or at a desired velocity.
Various embodiments of the present invention are intended to provide a nasal drug delivery device and/or a related method of delivering drugs nasally, typically using a breath actuation triggering approach.
In one embodiment, a nasal drug delivery device includes a housing having a spray port; a reservoir housing a liquidous medicament; and a selectively actuable pump supported by the housing and operatively connecting the reservoir to the spray port. A drive element (e.g., a spring) is operatively connected to the plunger and is elastically deformable between a higher potential energy state and a lower potential energy state. A breath actuated triggering mechanism associated with the housing includes a mouthpiece and a diaphragm, and controls the release of the drive element from the higher potential energy state to the lower potential energy state. A pressure differential across the diaphragm, higher towards the mouthpiece, causes the drive element to change from the higher state to the lower state, and the pump's plunger moves in response thereto to thereby cause the pump to supply the medicament to the spray port. A cocking lever can be pivotally mounted to the housing for movement between a first position and a second position, with movement of the cocking lever to the second position causing the drive element to elastically store potential energy. A second elastic element can act on the plunger in opposition to the firing element to provide a reset bias to the plunger. The triggering mechanism can further include a cam element pivotally attached to the housing and the diaphragm, wherein the cam element rotates in response to movement of the diaphragm. A follower element can be pivotally connected to the plunger for movement therewith and the follower element releasably engages the cam element. When the follower element is released from engagement with the cam element, the drive element is released to power the pump.
In another embodiment, a nasal drug delivery device includes a housing having a spray port; a reservoir housing a liquidous medicament; a selectively actuable pump supported by the housing and operatively connecting the reservoir to the spray port. An elastically deformable drive element is operatively connected to the plunger. A breath actuated triggering mechanism associated with the housing includes a mouthpiece and a diaphragm. The device is moveable between a cocked configuration and a delivery configuration. In the cocked configuration, the drive element is held in a first relatively higher potential energy state and the pump's plunger is relatively undepressed; in the delivery configuration, the drive element is in a relatively less potential energy state and the pump's plunger is relatively depressed. Blowing into the mouthpiece causes the diaphragm to move so as to release the drive element from the first state and thereby depress the plunger.
In another embodiment, a nasal drug delivery device includes a housing having a spray port; a reservoir housing a liquidous medicament; and a selectively actuable pump supported by the housing and operatively connecting the reservoir to the spray port. A cocking lever is pivotally mounted to the housing for movement between a first position and a second position. A first elastic element is operatively disposed between the plunger and the cocking lever, and movement of the cocking lever to the second position causes the elastic element to store energy. A trigger mechanism includes a diaphragm connected to the pump's plunger via a selectively breakable linkage. Inward movement of the diaphragm causes the linkage to break, thereby causing the pump's plunger to be depressed by the release of the energy stored in the elastic element.
In another embodiment, a method of administering a medicament nasally to a user includes providing a nasal delivery device, the nasal delivery device including: a housing having a spray port; a reservoir housing a liquidous medicament; a selectively actuable pump supported by the housing and operatively connecting the reservoir to the spray port; a cocking lever pivotally mounted to the housing for movement between a first position and a second position; and a first elastic element disposed operatively between the pump's plunger and the cocking lever. The method further includes storing energy in the first elastic element by moving the cocking lever to the second position while resisting movement of the plunger; and blowing into a mouthpiece associated with the housing, and, in response thereto, releasing the stored energy to depress the plunger to thereby cause delivery of a portion of the medicament into the nasal passages of a user. The releasing of stored energy can include deforming a diaphragm in response to blowing into the mouthpiece, and can further include breaking a selectively breakable linkage connecting the diaphragm to the plunger in response to inward deformation of the diaphragm.
In another embodiment, a method of administering a medicament nasally to a user includes providing a nasal delivery device including: a housing including a distal end portion and a proximal end portion and including a spray port disposed proximate the proximal end portion; the spray port configured to be inserted in a human user's nose; a reservoir housing a liquidous medicament; a manually powered pump supported by the housing and operatively connecting the reservoir to the spray port; an elastically deformable drive element operatively connected to the plunger; a breath actuated triggering mechanism associated with the housing and including a mouthpiece and a diaphragm; and the triggering mechanism controlling release of the drive element from a higher potential energy state to a lower potential energy state. The method further includes: disposing the proximal end portion proximate the user's face and the distal end portion distal from the user's face; a forward direction defined as extending from the distal end portion toward the proximal end portion; blowing into the mouthpiece in a direction generally opposite the forward direction so as to deform the diaphragm inwardly; in response to the diaphragm deformation, releasing the drive element to from the higher state to supply a force to depress a plunger of the pump; in response to the plunger depression, delivering a portion of the medicament into the nasal passages of the user by generating a spray of medicament from the spray port in a spray direction. A dot product of a first vector oriented in the forward direction and a second vector oriented in the spray direction is advantageously a non-zero positive value.
Other aspects of various embodiments of a related inventive device and other related methods are also disclosed in the following description. The various aspects can be used alone or in any combination, as is desired.
The present invention, in some embodiments, relates to a nasal drug delivery device 10 that includes a pump 50 that is breath actuated to supply drug-containing fluid to a spray port 44 for producing a spray of medicament. The pump 50 is prepared for use by the patient moving a cocking lever 80, and subsequently triggered by the patient blowing into a mouthpiece 130. The blowing action causes a diaphragm 126 to deform, which in turn causes a cam-based firing mechanism 90 to be displaced, resulting in a stored consistent amount of mechanical energy to be applied to the pump's plunger 60. Thus, the pump 50 has a substantially consistent actuation force across dosing events. Additionally, in some embodiments, the forward direction F of the device's housing 20 is oriented with respect to the device's direction of spray S so that the device 10 can be conveniently held by a patient for optimum results.
One embodiment of the nasal drug delivery device is shown in
The reservoir 70 is located in the housing 20 for storage of the liquidous medicament 5. While not required in all embodiments, the reservoir 70 is advantageously formed of a flexible material, such as polyolefin or silicone, so that the reservoir can collapse under atmospheric pressure as the medicament 5 is dispensed. Further, while the reservoir 70 is advantageously permanently disposed fully internal to the housing 20, the reservoir 70 can alternatively be only partially disposed in housing 20, and/or can be removable therefrom, as is desired.
Pump 50 is operatively connected to reservoir 70 and acts to pump medicament from reservoir 70 to spray port 44 when actuated. The pump 50 can be of any type known in the art, but advantageously takes the form of a positive displacement pump such as the elastomeric pump described in U.S. Pat. No. 6,223,746, the disclosure of which is incorporated herein by reference. In one embodiment, the pump 50 includes a main body 52 having a chamber 54, a pair of check valves 56a, 56b, and a plunger 60. See
As shown in
As can be seen in
Activation of the pump 50 results in the spraying of medicament 5 from spray port 44. However, because pump 50, in some embodiments, is a positive displacement pump, the force applied to plunger 60 affects the effective fluid pressure of the medicament 5 supplied to spray port 44 which, in turn, affects the particle size distribution of the resulting spray. Some embodiments of the device 10 therefore rely on an indirect actuation of plunger 60 using a compressed firing spring 99, with a consistent amount of energy stored in the compressed spring 99 immediately prior to firing the device, in order to provide a more consistent spray. In some embodiments, the spring 99 is initially compressed a repeatable amount by moving a cocking lever 80, and the spring force is released under the control of a trigger mechanism 100 that is breath actuated in that it is responsive to a patient blowing into a mouthpiece 130. Exemplary embodiments of suitable mechanisms are disclosed below. The disclosed embodiments are believed able to produce effective and repeatable doses of medicament 5 to be applied to the nasal mucosa and turbinates with far superior average particle size when compared with prior art devices. Moreover, the particle size of 20-40 um produced by such embodiments, though small enough to achieve rapid absorption in the nasal turbinates, is not so small that the medicament is readily transported past this region and into the pulmonary system. And, introduction of the medicament 5 to the pulmonary system is further inhibited by the triggering action that requires the patient to blow into the device 10 when the spray is delivered, thereby closing the soft palate in an action similar to that experienced during what is known as the “Valsalva maneuver”.
Referring to
Cap 92 typically takes the form of a simple cylindrical body closed on one end. The closed end of the cap 92 forms bearing wall 94, and an interior cavity 98 is formed by cap 92, bounded by the bearing wall 94 and associated sidewall 96. Firing spring 99 is disposed in this cavity 98, and abuts against the inner side of bearing wall 94. The other end of firing spring 99 abuts plunger 60. In some embodiments, cap 92 is intended to fit within the plunger, and the radially outer wall 66 of plunger 60 is advantageously sized so as to just receive sidewall 96 of cap 92 with a sliding fit. In other embodiments, cap 92 can fit over plunger 60, and sidewall 96 can include suitable slots for receiving mounting arm 118 and counter arm 16, discussed below.
As indicated above, firing spring 99 abuts against the inner side of bearing wall 94 on one end and plunger 60 on the other end. Advantageously, firing spring 99 is disposed in outer annular channel 64 and cavity 98. The firing spring 99 is elastically deformable. In a compressed state, firing spring 99 stores potential energy. When released, firing spring 99 releases some or all of this potential energy to return to a restored state that has relatively less potential energy. During the firing sequence, the potential energy released by firing spring 99 is used to drive plunger 60 toward pump main body 52 so as to make the pump 50 pump; as such, the firing spring 99 can sometimes be referred to as a drive spring or drive element. In the embodiment illustrated in
With further regard to
In a storage configuration (
Note that during the actuation process, firing spring 99 is held in a compressed state until the point of release is reached between tip 116 and lip 106, and this compressed state is repeatable across numerous actuations of the device 10. Thus, due to the mechanical arrangement of the firing mechanism 90 and plunger 60, the device 10 is capable of producing a repeatable spray of medicament. Further, the force supplied to the pump 50 from firing spring 99 is not directly proportional to the amount of force with which a patient might press a firing button. Instead, due to the relative positional triggering approach employed, the force applied to the plunger 60 is substantially constant. And, while the firing is triggered by the patient blowing into mouthpiece 130, the substantially constant pump actuation force is supplied to the plunger 60 despite potentially wide variations in how hard the patient is able to blow. Accordingly, both relatively weak and relatively strong patients can be supplied with a medicament spray that is consistent both in amount and in particle size distribution.
Some embodiments of the device 10 can include an optional dose counter 12, and plunger 60 can include a counter arm 16, in order to aid in keeping track of the number of actuations of pump 50. Any form of dose counter known in the art can be used, such as those described in U.S. Pat. Nos. 5,544,647 and 5,622,163, and U.S. patent application Ser. No. 10/625,359, the disclosures of which are incorporated herein by reference. Advantageously, the dose counter 12 is configured so as to be indexed by the sudden movement of counter arm 16 away from a contact 14 connected to the dose counter 12 to increment/decrement dose counter 12 in a conventional fashion. Other functionality can also be incorporated into the dose counter 12 using features known to those of skill in the art.
In some embodiments, a nosepiece cover 86 shaped and configured to cover the end of protrusion 40 can be provided for protecting the spray port 44 during periods of non-use. See
The discussion above has assumed that the device 10 includes a coil-type reset spring 69 and a coil-type firing spring 99 for applying their respective biases to plunger 60. However, it should be understood that any form of elastically deformable element known in the art (e.g., compressible foam, leaf spring, etc.) could be used for the desired biasing action, and conventional coil springs are not required in all embodiments. Indeed, while it is believed advantageous to use a conventional compressible element as the firing spring 99, some embodiments of the device 10 can use an extendible element (e.g., extension spring) or a deflectable element (beam-type spring element) alternatively or in addition thereto as the relevant drive element 99. Of course, there can also be multiple drive elements 99.
The discussion above has assumed that the device 10 includes a pivoting cocking lever 80 for loading the drive spring 99 with potential energy; however, such is not required in all embodiments. For example, in some embodiments, there can be no cocking lever 80; instead, the drive spring 99 can be loaded by the patient pressing directly on cap 92, and holding the cap 90 against a suitable stop during the firing sequence. With such an embodiment, the user would likely receive tactile feedback of the firing release of firing spring 99 as the patient blows into mouthpiece 130 to trigger the device. Note that with such an embodiment, the pump action of pump 50, and therefore the resulting spray characteristics, are still not determined by the rate that the cap 90 is pressed. Instead, assuming that the patient has a minimal amount of strength to press/hold cap 92 to/at the desired location, a repeatable amount of pressing force is supplied to plunger 60.
The present invention can be carried out in other specific ways than those herein set forth without departing from the scope and essential characteristics of the invention. Further, the various aspects of the disclosed device and method can be used alone or in any combination, as is desired. The disclosed embodiments are, therefore, to be considered in all respects as illustrative and not restrictive, and all changes coming within the meaning and equivalency range of the appended claims are intended to be embraced therein.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/US2008/059056 | 4/1/2008 | WO | 00 | 4/23/2010 |
| Number | Date | Country | |
|---|---|---|---|
| 60909569 | Apr 2007 | US |
