U.S. patent application number 17/184247 was filed with the patent office on 2021-06-17 for dry powder inhaler dose counters.
The applicant listed for this patent is Adamis Pharmaceuticals Corporation. Invention is credited to Michael K. Domroese, Peter D. Hodson, Bryan E. Rolfs, Benjamin L. Rush, Stephen W. Stein, Jonathan D. Toback.
Application Number | 20210178089 17/184247 |
Document ID | / |
Family ID | 1000005417944 |
Filed Date | 2021-06-17 |
United States Patent
Application |
20210178089 |
Kind Code |
A1 |
Rolfs; Bryan E. ; et
al. |
June 17, 2021 |
DRY POWDER INHALER DOSE COUNTERS
Abstract
Dry powder inhaler dose counters capable of making a display
move swiftly between digits, in contrast to the progressive
movement that occurs in simple gearing mechanisms.
Inventors: |
Rolfs; Bryan E.; (Chicago,
IL) ; Rush; Benjamin L.; (Wilmette, IL) ;
Toback; Jonathan D.; (Chicago, IL) ; Hodson; Peter
D.; (Bracknell, GB) ; Stein; Stephen W.; (Lino
Lakes, MN) ; Domroese; Michael K.; (Woodbury,
MN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Adamis Pharmaceuticals Corporation |
San Diego |
CA |
US |
|
|
Family ID: |
1000005417944 |
Appl. No.: |
17/184247 |
Filed: |
February 24, 2021 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
15971924 |
May 4, 2018 |
10953166 |
|
|
17184247 |
|
|
|
|
14817047 |
Aug 3, 2015 |
9987442 |
|
|
15971924 |
|
|
|
|
13320761 |
Mar 6, 2012 |
9125999 |
|
|
PCT/US2010/035129 |
May 17, 2010 |
|
|
|
14817047 |
|
|
|
|
61179231 |
May 18, 2009 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M 15/0025 20140204;
G06M 1/04 20130101; A61M 15/0045 20130101; A61M 2202/064 20130101;
A61M 15/0065 20130101; A61M 15/0043 20140204; A61M 15/0055
20140204; A61M 15/0075 20140204; G06M 1/045 20130101; A61M 15/0026
20140204; A61M 15/0046 20140204; A61M 15/0091 20130101; A61M
15/0008 20140204; A61M 15/0071 20140204; A61M 15/0051 20140204 |
International
Class: |
A61M 15/00 20060101
A61M015/00; G06M 1/04 20060101 G06M001/04 |
Claims
1. A method of treating a respiratory disorder comprising
administering to a patient in need thereof an active agent with a
dry powder inhalation device comprising: a housing defining a
chamber; a patient port in communication with said chamber; an
elongate carrier carrying medicament; an advancement mechanism for
advancing a length of the elongate carrier into the chamber; a
displacement sensor that advances in association with continuous
advancement of the elongate carrier; and a transfer component that
converts the advancement of the displacement sensor into
intermittent motion of a units dose display.
2. The method according to claim 1, wherein the displacement sensor
has a range of movably engaged positions wherein the displacement
sensor movably engages the transfer component, and the dry powder
inhalation device further comprises a discrete alignment mechanism
capable of moving the displacement sensor backwards to one of a
plurality of spatially defined positions that are not within said
range of movably engaged positions.
3. The method according to claim 2 wherein the discrete alignment
mechanism comprises a reverse pawl wheel capable of engaging with a
post fixed to the device housing.
4. The method according to claim 3 wherein the reverse pawl wheel
comprises two pawl arms.
5. The method according to claim 4 wherein the discrete alignment
mechanism comprises a slot in the reverse pawl wheel that is
reversibly engageable with a post fixed to the device housing.
6. The method according to claim 1 wherein the advancement
mechanism comprises a rotatable mouthpiece cover.
7. The method according to claim 1 wherein the advancement
mechanism comprises an uptake spool.
8. The method according to claim 7 wherein the displacement sensor
is driven by gears on the uptake spool.
9. The method according to claim 1 wherein the displacement sensor
comprises a rotatable gear.
10. The method according to claim 1 wherein the transfer component
comprises a Geneva wheel.
11. The method according to claim 10 wherein the Geneva wheel has
scallops along its outer edge.
12. The method according to claim 1 wherein the units dose display
is a geared units dose wheel with numerical indicia on one face of
the wheel.
13. The method according to claim 12 further comprising a tens dose
display comprising a geared tens dose wheel coupled to the units
dose wheel and wherein the units dose display and the tens dose
display cooperate to indicate a number of doses remaining in the
device.
14. The method according to claim 13 wherein the tens dose wheel
has scallops along its outer edge.
15. The method according to claim 1 wherein the elongate carrier is
a dimpled tape.
16. The method according to claim 1 wherein the displacement sensor
moves in association with movement of the elongate carrier.
17. The method according to claim 1, wherein said active agent
comprises at least one of albuterol, levalbuterol, terbutaline,
fenoterol, metaproterenol, isoproterenol, isoetharine, bitolterol,
epinephrine, tulobuterol, bambuterol, reproterol, adrenaline,
ipratropium, oxitropium, tiotropium, daratropium, aclidinium,
glyciopyrronium, beclomethasone, betamethasone, butixocort,
flunisolide, budesonide, mometasone, ciclesonide, rofleponide,
aminophylline, dyphylline, theophylline, cromolyn sodium,
nedocromil sodium, ketotifen, azelastine, ergotamine, cyclosporine,
salmeterol, fluticasone, formoterol, arformoterol, procaterol,
indacaterol, TA2005 (carmoterol), omalizumab, montelukast,
zafirlukast, betamethasone sodium phosphate, dexamethasone,
dexamethasone sodium phosphate, dexamethasone acetate, prednisone,
methylprednisolone acetate, oglemilast, zileuton, insulin,
atropine, prednisolone, benzphetamine, chlorphentermine,
amitriptyline, imipramine, clonidine, actinomycin c, bromocriptine,
fentanyl, buprenorphine, pentamidine, calcitonin, leuprolide,
alpha-1-antitrypsin, interferons, propranolol, lacicortone,
triamcinolone, dinoprost, xylometazoline, diazepam, lorazepam,
folic acid, nicotinamide, clenbuterol, ethinyloestradiol,
levonorgestrel, and pharmaceutically acceptable salts and esters
thereof such as albuterol sulfate, formoterol fumarate, salmeterol
xinafoate, aclidinium bromide, glycopyrronium bromide,
beclomethasone dipropionate, triamcinolone acetonide, fluticasone
propionate, fluticasone furoate, tiotropium bromide, leuprolide
acetate or mometasone furoate.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 14/817,047, filed Aug. 3, 2015, which is a
continuation of U.S. patent application Ser. No. 13/320,761, filed
Mar. 6, 2012, which is the U.S. national phase of International
Application No. PCT/US2010/035129, filed May 17, 2010, which claims
priority to U.S. Provisional Patent Application 61/179,231, filed
May 18, 2009. The entire contents of these applications are
incorporated herein by reference.
BACKGROUND
Field
[0002] This application relates to dry powder inhalers (DPIs) and
in particular, to dose counters for dry powder inhalers.
Description of the Related Art
[0003] Asthma and other respiratory diseases have long been treated
by the inhalation of appropriate medicaments. For many years the
two most widely used and convenient choices of treatment have been
the inhalation of medicament from a drug solution or suspension in
a pressurized metered dose inhaler (pMDI), or inhalation of
powdered drug, generally admixed with an excipient, from a dry
powder inhaler (DPI). Following strong concern about the link
between depletion of the earth's ozone layer and chlorofluorocarbon
(CFC) emissions, the use of these materials in pressurized inhalers
is being phased out and interest in DPI systems has been
stimulated.
[0004] Current regulatory guidance in some parts of the world
recommends that a medicinal inhaler include a dose-counting device
so that a patient may be aware when a device is nearing the end of
its recommended number of actuations. It is desired that a dose
counter be as nearly 100 percent reliable as possible and, in
particular, that a device avoid undercounting. That is, the device
should not deliver a dose without advancement of the counter, since
this could lead a patient to believe there is more medication left
in the device than actually remains.
[0005] Dose counters for dry powder inhalers are well known in the
state of the art, including those described in, for example, U.S.
Pat. No. 5,582,162 (Petersson), U.S. Pat. No. 5,590,645 (Davies et
al.), U.S. Pat. No. 7,107,988 (Pinon et al.), U.S. Pat. No.
7,322,352 (Minshull et al.), and WO 2005/079727 (Augustyn et al.).
In practice most DPIs use either bulk powder reservoirs or
individual pre-measured doses sealed within individual containers
in the form of capsules or blisters, such as blister packs and
blister strips. In a typical device with capsules or blisters it is
generally sufficient to simply count the capsules or blisters one
by one as the device is actuated and they are used. In a typical
reservoir device there is generally a metering step, such as
rotation of a dose cup from a position inside the reservoir to a
position within an airflow chamber, and dose counting can be done
by simply counting the number of rotations of the dose cup.
SUMMARY
[0006] According to one aspect of the present description there is
provided a dry powder inhalation device comprising a housing
defining a chamber, a patient port in communication with said
chamber, an elongate carrier carrying medicament, an advancement
mechanism for advancing a length of the elongate carrier into the
chamber, a displacement sensor that advances in association with
continuous advancement of the elongate carrier, and a transfer
component that converts the advancement of the displacement sensor
into intermittent motion of a units dose display.
[0007] The displacement sensor of a dry powder inhaler in
accordance with the first aspect described herein may
advantageously have a range of positions where it movably engages
the transfer component. The inhaler may further comprise a discrete
alignment mechanism capable of moving the displacement sensor
backwards to one of a plurality of spatially defined positions that
are not within said range of movably engaged positions. Dependent
claims define further embodiments.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] In the accompanying drawings:
[0009] FIG. 1 represents a partial rear view of an exemplary device
wherein the rear housing has been omitted for illustrative
purposes.
[0010] FIG. 2 represents a partial rear view of the exemplary
device wherein the rear housing and mouthpiece cover have been
omitted for illustrative purposes.
[0011] FIG. 3 represents a partial rear view of an exemplary device
wherein the rear housing has been omitted for illustrative purposes
and the device is shown with its mouthpiece cover in the fully
opened position.
[0012] FIG. 4 represents a front view of the exemplary device, with
the units wheel and tens wheel shown in outline.
[0013] FIG. 5a represents a partial rear view of a detailed portion
of the exemplary device in its closed position.
[0014] FIG. 5b represents a partial isometric near-to-rear cross
sectional view of a detailed portion of the exemplary device in its
closed position.
[0015] FIG. 5c represents an isometric near-to-front view of a
detailed portion of the exemplary device in its closed
position.
[0016] FIG. 5d represents an enlarged view of a detailed portion of
FIG. 5c.
[0017] FIGS. 6a, 6b, 6c to 9a, 9b, 9c represent views corresponding
to FIGS. 5a, 5b, 5c at different positions between closed and fully
open.
[0018] FIG. 10 represents an isometric near-to-rear view of a
detailed portion of the exemplary device.
[0019] FIG. 11 represents an isometric near-to-front view of a
detailed portion of the exemplary device.
[0020] FIG. 12a represents a partial rear view of a detailed
portion of a second exemplary device in its closed position.
[0021] FIG. 12b represents a partial isometric near-to-rear cross
sectional view of a detailed portion of the second exemplary device
in its closed position.
DETAILED DESCRIPTION
[0022] A problem that had not previously been appreciated in the
art is that, where a dry powder inhalation device dispenses
medicament on an elongate carrier (e.g., an elongate strip) by
length, counting of doses corresponding to dispensed lengths is not
straightforward. Briefly, the count display can lodge between
digits, leading to confusion of the user even if a display window
large enough to show the digits on either side is employed.
[0023] Inhalation devices according to the description are able to
make the display move swiftly between digits, in contrast to the
progressive movement that would occur in simple gearing mechanisms.
Where the operation of an inhalation device involves a repeated
advancing movement e.g., movement of a spool taking up an elongate
carrier bearing medicament for dosing, arranging for swift movement
between digits of a dose counter engaged with the spool provides a
display showing an individual units count digit, rather than units
count digits slightly offset from a viewing window.
[0024] Certain embodiments of the description provide mechanisms to
prevent the display getting out of step with the dosing due to
accumulation of small variations in the advancement per dose, or
due to the patient only partially advancing the dispensing
mechanism. Such small variations can arise due to relative
positions of ratchets and pawls at the end of a motion during which
a pawl slips over a ratchet. Surprisingly, these embodiments employ
larger variations in the relative positions of a pawl and a ratchet
at the end of motion, and yet provide a precise count point in the
dispensing operation at which digital advancement occurs. This
allows either one digit or the next to be displayed even if a
partial dispensing operation was performed close to this count
point, whilst retaining a memory of what partial dose was dispensed
in order to keep the tally accurate.
[0025] Thus, the dry powder inhalation devices of the description
provide digital counting mechanisms that are accurate and do not
lodge between digits during operation.
[0026] FIG. 1 represents a partial rear view of an exemplary dry
powder inhaler (10) in its closed position wherein the rear housing
has been omitted for illustrative purposes. FIG. 2 represents a
corresponding view of the inhaler (10) wherein the mouthpiece cover
(301) has been omitted. The inhaler (10) includes a flow chamber
(200) and a patient port, in particular in the form of a mouthpiece
(300), in communication with said chamber. The patient port is not
visible in FIG. 1, because in the closed position of the
illustrated inhaler the mouthpiece is covered by the cover (301),
but it is shown in FIG. 3 in which the cover has been fully opened.
The inhaler (10) also includes an elongate carrier (100) preloaded
with finely divided powder comprising a biologically active
substance (not visible). Preferably, the elongate carrier (e.g., an
elongate strip) is in the form of a tape.
[0027] The elongate carrier can be provided in a variety of forms,
such as a tape, web, belt or cord. Desirably the carrier is
provided in the form of a tape or a web. The elongate carrier may
have any ratio of length to width but the ratio is generally
greater than 5 to 1, usually greater than 10 to 1, more
particularly from about 100:1 to about 1000:1. The elongate carrier
may typically have a width of 5 mm to 20 mm, e.g., 10 mm. Its
thickness may typically be from 75 microns to 500 microns,
particularly 100 microns to 250 microns, more particularly from
about 120 microns to 175 microns. Optionally, the elongate carrier
may be provided with a lid component, for example to cover and/or
seal off individual doses pre-loaded on the carrier.
[0028] The powder comprising a biologically active substance,
typically a medicament, is releasably retained on a surface of the
elongate carrier. The powder may be retained on the elongate
carrier by attraction forces, such as electrostatic attraction, van
der Waals forces, physical attraction; mechanical binding; and/or
wedging. Alternatively as indicated supra powder may be retained on
the elongate carrier by covering the powder using a lid component;
however it is desirable not to have the pre-loaded powder on the
elongate carrier covered and sealed with a lid component. To
facilitate favorable release characteristics, it is desirable not
to retain the powder on the elongate carrier via adhesives or
glues. The aforesaid expression "mechanical binding" generally
refers to powder particles being held onto the elongate carrier by
intrinsic mechanical means of the elongate carrier material, e.g.,
within the entanglement of fibers of a nonwoven web. The expression
"wedging" generally refers to loading powder particles within/into
particular structures of the elongate carrier (e.g., micro-dimples
provided in a plastic elongate carrier, or porous spaces of a
nonwoven elongate carrier). One or more surfaces of the elongate
carrier and optionally the interior of the elongate carrier may be
configured to assist in retaining the particles of powder.
[0029] An elongate carrier may be constructed from one or more of a
wide range of natural and synthetic materials e.g., polyethylene,
polypropylene, polyester e.g., polyethylene terephthalate,
polytetrafluoroethylene or a co-polymer thereof, ethylene vinyl
alcohol, or cellulose. The materials may be in the form of
non-woven fibrous materials, loose weave materials or fabrics,
materials having a surface pile, films, microporous materials,
microgrooved materials, cords of twisted fibers, or any other
suitable material or composites of more than one material.
Desirably an elongate carrier is constructed of a material or a
material composite where small surface depressions, dimples,
grooves, recesses, interstices, apertures or embossed surface
structures having a typical size of equal to or less than 500
microns in either depth or height and of greater than 0.1 microns
in at least one other dimension are provided to help to retain the
particles of powder. Various materials for elongate carriers as
well as particular forms of carriers suitable for use herein are
disclosed in U.S. Pat. No. 5,619,984 (Hodson et al.), the contents
of said patent in its entirety being incorporated here by
reference.
[0030] Finely divided powders used in the devices described herein
generally have a mass median particle diameter of 10 microns or
less. More suitably, said mass median diameter is 7 microns or
less, even more suitably 5 microns or less, and most suitably said
mass median diameter is in the range 1 to 3 microns, with at least
90% by mass of the particles having diameters below 5 microns.
[0031] The powders may be micronized, e.g., by (i) using a fluid
energy mill driven by compressed air, such as shown in `Drug
Delivery to the Respiratory Tract` ed. D. Ganderton and T. Jones,
publ. Ellis Horwood, Chichester (1987) pages 89-90, or (ii) by
repeated stepwise millings or (iii) by use of a closed loop milling
system.
[0032] As indicated supra, desirably finely divided powder is
filled into a plurality of microdepressions in the surface of an
elongate carrier, in particular a flexible elongate carrier, such
as a web or a tape. Depressions may be suitably spaced at an
interval of about 20 to 2000 microns, more suitably at an interval
of about 300 to 2000 microns. Depressions may suitably number from
about 25 to 1000 per cm2 of the web. The volume of each depression
and the spacing or number of the depressions will depend upon the
particular desired application of the resulting filled web and/or
elongate carrier, and in the case of biologically active substances
(e.g., medicaments) the potency of the particular substance and the
area of the web material intended to provide a single dose of the
substance. As the web will typically have a fixed width, one may
refer to a corresponding length of web material intended to provide
a single dose of substance.
[0033] Typically it is desirable that the elongate carrier material
(e.g., web material) has a substantially uniform depression volume
per unit area when considered on a scale of the area of a single
dose or other functional unit. For example, such a dose area might
have 200 to 2000 discrete microdepressions, each of about 45
microns depth and about 150 microns diameter. Advantageously, the
rows of microdepressions along the longitudinal axis of the
elongate carrier do not lie exactly parallel with the axis, but
instead lie skewed at a small angle (e.g., 0.5.degree. to
2.degree.) to it, in order to avoid "quantization effects" caused
by lateral variability in the slitting positions. The skew angle
can be chosen appropriate to the microdepression spacing distance
and the desired slit width, such that an exact total
micro-depression volume is present on each (e.g., 20 mm.times.10
mm) dose area, no matter where slitting occurs, laterally.
[0034] Preferably, the microdepressions are provided by cast
embossing of a low density polyethylene (LDPE) layer using a
photolithographically patterned and etched, or a diamond machined,
patterning roller. Suitably, the aforesaid LDPE layer is provided
on a paper backing or a paper/LDPE laminate backing (with the paper
between the two LDPE layers).
[0035] Such filled elongate carriers are particularly conveniently
used in the administration of biologically active substances, in
particular medicaments by inhalation. Moreover, elongate carriers
having microdepressions can be substantially accurately and
uniformly filled with such finely divided powders e.g., through
methods disclosed in WO 2007/112267 (Hodson and Wilby), the content
of which is incorporated in its entirety by reference, thus
allowing for accurate and uniform release of doses of biologically
active substances.
[0036] For delivery by inhalation, suitable medicaments include any
drug or combination of drugs that may be administered by
inhalation, that is a solid or that may be incorporated in a solid
carrier. Suitable drugs include those for the treatment of
respiratory disorders, e.g., bronchodilators, anti-inflammatories
(e.g., corticosteroids) anti-allergies, anti-asthmatics,
anti-histamines, and anti-cholinergic agents. Other drugs such as
anorectics, anti-depressants, anti-hypertensive agents,
anti-neoplastic agents, anti-tussives, anti-anginals,
anti-infectives (e.g., antibacterials, antibiotics, anti-virals),
anti-migraine drugs, anti-peptics, dopaminergic agents, analgesics,
beta-adrenergic blocking agents, cardiovascular drugs,
hypoglaecemics, immunomodulators, lung surfactants, prostaglandins,
sympathomimetics, tranquilizers, steroids, vitamins and sex
hormones, vaccines and other therapeutic proteins and peptides may
be employed for delivery by inhalation.
[0037] It is preferred for delivery by inhalation that the
medicament employed exhibits a potency which permits a single dose
to be loaded onto the elongate carrier in an area of less than
about 25 cm2 and preferably less than about 5 cm2. More preferred
is an elongate carrier containing a drug in such a manner and of
such a type that between 0.25 and 2.5 cm2, most preferably between
1.5 and 2.25 cm2, of the elongate carrier will contain a single
dose when used in a device such as those described in U.S. Pat.
Nos. 5,408,994 or 5,619,984. Stated differently, given that a
filled elongate carrier may conveniently carry between about 25 and
500 .mu.g of powder per cm2, the potency of the medicament will
preferably be such that a single dose may be carried on the
above-stated 0.25 to 2.5 cm2 of elongate carrier.
[0038] Exemplary drugs which may be employed for delivery by
inhalation include but are not limited to: albuterol, levalbuterol,
terbutaline, fenoterol, metaproterenol, isoproterenol, isoetharine,
bitolterol, epinephrine, tulobuterol, bambuterol, reproterol,
adrenaline, ipratropium, oxitropium, tiotropium, daratropium,
aclidinium, glyciopyrronium, beclomethasone, betamethasone,
butixocort, flunisolide, budesonide, mometasone, ciclesonide,
rofleponide, aminophylline, dyphylline, theophylline, cromolyn
sodium, nedocromil sodium, ketotifen, azelastine, ergotamine,
cyclosporine, salmeterol, fluticasone, formoterol, arformoterol,
procaterol, indacaterol, TA2005 (carmoterol), omalizumab,
montelukast, zafirlukast, betamethasone sodium phosphate,
dexamethasone, dexamethasone sodium phosphate, dexamethasone
acetate, prednisone, methylprednisolone acetate, oglemilast,
zileuton, insulin, atropine, prednisolone, benzphetamine,
chlorphentermine, amitriptyline, imipramine, clonidine, actinomycin
c, bromocriptine, fentanyl, buprenorphine, pentamidine, calcitonin,
leuprolide, alpha-1-antitrypsin, interferons, propranolol,
lacicortone, triamcinolone, dinoprost, xylometazoline, diazepam,
lorazepam, folic acid, nicotinamide, clenbuterol,
ethinyloestradiol, levonorgestrel, and pharmaceutically acceptable
salts and esters thereof such as albuterol sulfate, formoterol
fumarate, salmeterol xinafoate, aclidinium bromide, glycopyrronium
bromide, beclomethasone dipropionate, triamcinolone acetonide,
fluticasone propionate, fluticasone furoate, tiotropium bromide,
leuprolide acetate and mometasone furoate.
[0039] Further drugs that may also be delivered by inhalation
include but are not limited to aspirin, acetaminophen, ibuprofen,
naproxen sodium, buprenorphine hydrochloride, propoxyphene
hydrochloride, propoxyphene napsylate, meperidine hydrochloride,
hydromorphone hydrochloride, morphine sulfate, fentanyl citrate,
oxycodone hydrochloride, codeine phosphate, dihydrocodeine
bitartrate, pentazocine hydrochloride, hydrocodone bitartrate,
levorphanol tartrate, diflunisal, naltrexone, oxycodone,
sufentanil, remifentanil, diamorphine, trolamine salicylate,
methadone hydrochloride, nalbuphine hydrochloride, nalorphine,
tetrahydrocannabinol, mefenamic acid, butorphanol tartrate, choline
salicylate, butalbital, phenyltoloxamine citrate, diphenhydramine
citrate, methotrimeprazine, cinnamedrine hydrochloride,
meprobamate, ergotamine tartrate, propanolol hydrochloride,
isometheptene mucate, dichloralphenazone, sumatriptan, rizatriptan,
zolmitriptan, naratriptan, eletriptan, barbiturates (e.g.,
pentobarbital, pentobarbital sodium, secobarbital sodium),
benzodiazapines (e.g., flurazepam hydrochloride, triazolam,
tomazeparm, midazolam hydrochloride, lorazepam, buspirone
hydrochloride, prazepam, chlordiazepoxide hydrochloride, oxazepam,
clorazepate dipotassium, diazepam, temazepam), lidocaine,
prilocaine, xylocaine, beta-adrenergic blockers, calcium channel
blockers (e.g., nifedipine, diltiazem hydrochloride, and the like),
diuretics (e.g., amiloride, furosemide), nitrates (e.g.,
nitroglycerin, isosorbide dinitrate, pentaerythritol tetranitrate,
erythrityl tetranitrate), hydroxyzine pamoate, hydroxyzine
hydrochloride, alprazolam, droperidol, halazepam, chlormezanone,
haloperidol, loxapine succinate, loxapine hydrochloride,
thioridazine, thioridazine hydrochloride, thiothixene, fluphenazine
hydrochloride, fluphenazine decanoate, fluphenazine enanthate,
trifluoperazine hydrochloride, chlorpromazine hydrochloride,
perphenazine, lithium citrate, prochlorperazine, lithium carbonate,
bretylium tosylate, esmolol hydrochloride, verapamil hydrochloride,
amiodarone, encainide hydrochloride, digoxin, digitoxin, mexiletine
hydrochloride, disopyramide phosphate, procainamide hydrochloride,
quinidine sulfate, quinidine gluconate, quinidine
polygalacturonate, flecainide acetate, tocainide hydrochloride,
lidocaine hydrochloride, phenylbutazone, sulindac, penicillamine,
salsalate, piroxicam, azathioprine, indomethacin, meclofenamate
sodium, gold sodium thiomalate, ketoprofen, auranofin,
aurothioglucose, tolmetin sodium, colchicine, allopurinol, heparin,
heparin sodium, warfarin sodium, urokinase, streptokinase,
altoplase, aminocaproic acid, pentoxifylline, empirin, ascriptin,
valproic acid, divalproate sodium, phenytoin, phenytoin sodium,
clonazepam, primidone, phenobarbitol, phenobarbitol sodium,
carbamazepine, amobarbital sodium, methsuximide, metharbital,
mephobarbital, mephenytoin, phensuximide, paramethadione, ethotoin,
phenacemide, secobarbitol sodium, clorazepate dipotassium,
trimethadione, ethosuximide, doxepin hydrochloride, amoxapine,
trazodone hydrochloride, amitriptyline hydrochloride, maprotiline
hydrochloride, phenelzine sulfate, desipramine hydrochloride,
nortriptyline hydrochloride, tranylcypromine sulfate, fluoxetine
hydrochloride, doxepin hydrochloride, imipramine hydrochloride,
imipramine pamoate, nortriptyline, amitriptyline hydrochloride,
isocarboxazid, desipramine hydrochloride, trimipramine maleate,
protriptyline hydrochloride, hydroxyzine hydrochloride,
diphenhydramine hydrochloride, chlorpheniramine maleate,
brompheniramine maleate, clemastine, azelastine, loratidine,
cyproheptadine hydrochloride, terfenadine citrate, clemastine,
triprolidine hydrochloride, carbinoxamine maleate, diphenylpyraline
hydrochloride, phenindamine tartrate, lamivudine, abacavir,
acyclovir, gancyclovir, valganciclovir, cidofovir, foscarnet,
azatadine maleate, tripelennamine hydrochloride,
dexchlorpheniramine maleate, methdilazine hydrochloride,
trimprazine tartrate, trimethaphan camsylate, phenoxybenzamine
hydrochloride, pargyline hydrochloride, deserpidine, diazoxide,
guanethidine monosulfate, minoxidil, rescinnamine, sodium
nitroprusside, rauwolfia serpentina, alseroxylon, phentolamine
mesylate, reserpine, calcitonin, parathyroid hormone, acitretin,
amikacin sulfate, aztreonam, benzydamine, calcipotriol,
chloramphenicol, chloramphenicol palmitate, chloramphenicol sodium
succinate, ciprofloxacin hydrochloride, clindamycin hydrochloride,
clindamycin palmitate, clindamycin phosphate, efalizumab,
reslizumab, mepolizumab, anrukinzumab, metronidazole, metronidazole
hydrochloride, gentamicin sulfate, lincomycin hydrochloride,
tobramycin sulfate, tacrolimus, vancomycin hydrochloride, polymyxin
B sulfate, colistimethate sodium, colistin sulfate, tetracycline,
griseofulvin, keloconazole, interferon gamma, zidovudine,
amantadine hydrochloride, ribavirin, acyclovir, pentamidine e.g.,
pentamidine isoethionate, cephalosporins (e.g., cefazolin sodium,
cephradine, cefaclor, cephapirin sodium, ceftizoxime sodium,
cefoperazone sodium, cefotetan disodium, cefutoxime axotil,
cefotaxime sodium, cefadroxil monohydrate, ceftazidime, cephalexin,
cephalothin sodium, cephalexin hydrochloride monohydrate,
cefamandole nafate, cefoxitin sodium, cefonicid sodium, ceforanide,
ceftriaxone sodium, ceftazidime, cefadroxil, cephradine, cefuroxime
sodium, and the like), penicillins (e.g., ampicillin, amoxicillin,
penicillin G benzathine, cyclacillin, ampicillin sodium, penicillin
G potassium, penicillin V potassium, piperacillin sodium, oxacillin
sodium, bacampicillin hydrochloride, cloxacillin sodium,
ticarcillin disodium, azlocillin sodium, carbenicillin indanyl
sodium, penicillin G potassium, penicillin G procaine, methicillin
sodium, nafcillin sodium, and the like), erythromycins (e.g.,
erythromycin ethylsuccinate, erythromycin, erythromycin estolate,
erythromycin lactobionate, erythromycin siearate, erythromycin
ethylsuccinate, and the like), tetracyclines (e.g., tetracycline
hydrochloride, doxycycline hyclate, minocycline hydrochloride,
GM-CSF, ephedrine, pseudoephedrine, ammonium chloride, androgens
(e.g., danazol, testosterone cypionate, fluoxymesterone,
ethyltostosterone, testosterone enanihate, methyltestosterone,
fluoxymesterone, testosterone cypionate), estrogens (e.g.,
estradiol, estropipate, conjugated estrogens), progestins (e.g.,
methoxyprogesterone acetate, norethindrone acetate), levothyroxine
sodium, human insulin, purified beef insulin, purified pork
insulin, glyburide, chlorpropamide, glipizide, tolbutamide,
tolazamide, rosiglitazone, pioglitazone, troglitazone, clofibrate,
dextrothyroxine sodium, probucol, lovastatin, rosuvastatin, niacin,
DNase, alginase, superoxide dismutase, lipase, calcitonion,
alpha-1-antitrypsin, human growth hormone, interferons, sense or
anti-sense nucleic acids encoding any protein suitable for delivery
by inhalation, erythropoietin, famotidine, cimetidine, ranitidine
hydrochloride, omeprazole, esomeprazole, lanzoprazole, meclizine
hydrochloride, nabilone, prochlorperazine, dimenhydrinate,
promethazine hydrochloride, thiethylperazine, scopolamine,
sildenafil, vardenafil, cilomilast, imiquimod or resiquimod. Where
appropriate, these drugs may be delivered in alternative salts
forms.
[0040] The medicament may comprise one or more drugs, having one or
more particulate forms, and may include one or more physiologically
acceptable or inert excipients.
[0041] As shown in the exemplary embodiment illustrated in FIGS. 1
to 3, the elongate carrier (100) may be stored initially on a
supply spool (102) and advanced onto an uptake spool (400) during
use of the inhaler. In particular, the rotational motion of the
mouthpiece cover (301) during opening is coupled to the uptake
spool (400) and causes advancement of the elongate carrier (100).
During use of the inhaler, in general, a portion of the elongate
carrier is advanced to within the flow chamber so that the powder
associated with an advanced length of the elongate carrier can be
and is, upon actuation, released from the elongate carrier for
inhalation by the patient through the patient port. In a preferred
embodiment, a length of a predetermined size of the elongate
carrier comprises a single dose of medicament.
[0042] A typical total length of elongate carrier would usually be
greater than that shown on the supply spool in FIGS. 1 to 3, but
the length shown is for ease of illustration. The elongate carrier
(100) with its preloaded finely divided powder providing a
plurality of doses is housed within a compartment (105), with the
compartment being configured so that the preloaded doses are sealed
within the compartment and such that the elongate carrier may be
advanced from the compartment to the flow chamber (200) through an
exit (107). As shown in FIGS. 1 and 2, where the inhaler is in its
closed position, the exit (107) is closed on the elongate carrier.
In use, however, the exit may be opened by movement of the pivoting
component (112), which pivots downwards when the mouthpiece cover
is opened.
[0043] As shown in FIG. 4, the inhaler includes a dose counter that
indicates the number of doses remaining in the device which is
visible through a window (320) in the outer housing (330). The
dashed lines show the (hidden) positions of a units wheel (450) and
a tens wheel (460) which cooperate to display a dose readout, in
this case the number `106`. Further details of the operation of the
dose counter will be described with reference to FIGS. 5a,b,c to
9a,b,c.
[0044] FIG. 5a represents a partial isometric near-to-rear view of
a detailed portion of the inhaler in its closed position. The
elongate carrier (100) is shown attached to an uptake spool (400).
As described in more detail below, the uptake spool (400) may be
driven forward or advanced (clockwise as drawn) by a forward pawl
wheel (402) and in particular by two forward pawl wheel arms (404,
405) that engage with a first set of teeth (one tooth of which is
denoted 420a) on the inner hub of the uptake spool (400) that serve
as ratchet teeth. The uptake spool (400) may also be engaged by a
reverse pawl wheel (412) having two reverse pawl wheel arms (414,
415) that may be better seen in the view shown in FIG. 5b. The
reverse pawl wheel arms (414, 415) engage with a second set of
ratchet teeth (one tooth of which is shown as 421a) on the inner
hub of the uptake spool (400). The second set of ratchet teeth is
also clearly visible in FIG. 5c and the tip of one tooth (420b) on
the first set of ratchet teeth is just visible in FIG. 5c. The tip
of tooth (420b) may be seen more clearly in FIG. 5d, which is an
enlarged view of a detailed portion of FIG. 5c. Referring back to
FIG. 5b, a post (416) that serves to limit the rotation of the
reverse pawl wheel (412) is shown engaged with the lower (as drawn)
surface of a slot (417) in the reverse pawl wheel (412). The post
(416) has a fixed position in relation to the outer housing (330)
and can thus be used to fix the extreme rotational positions of the
reverse pawl wheel (412), in particular the extreme anticlockwise
position shown in FIG. 5b, and to allow for limited movement of the
reverse pawl wheel (412).
[0045] FIG. 5c represents an isometric near-to-front view of a
detailed portion of the inhaler showing the relationship of the
uptake spool (400) to the additional parts of the dose counting
mechanism. The uptake spool (400) has spool gear teeth (424) that
engage with sensor gear teeth (432) on the reverse side of a
displacement sensor wheel (430), which may be seen in the rear view
shown in FIG. 10. The displacement sensor wheel (430) can engage a
Geneva wheel (440) through a pin (434) which can interact with
lobes (442), shown in FIG. 10, on the reverse side of the Geneva
wheel (440). The Geneva wheel (440) has concave cut-outs or
scallops (443), shown in FIG. 10, along the outer edge of the lobes
(442). These scallops (443) mate with a central hub (438) on the
displacement sensor wheel (430), shown in FIG. 11 as well as FIGS.
5c-9c, and prevent the Geneva wheel (440) from rotating unless the
displacement sensor wheel (430) is rotated so that the pin (434) is
interacting with the Geneva wheel (440), in which alignment a
cut-out region (439) allows the Geneva wheel (440) to rotate.
[0046] The Geneva wheel (440) can in turn drive a units wheel (450)
via Geneva gear teeth (444) that interact with units wheel gear
teeth (452), shown in FIG. 10, on the reverse side of the units
wheel (450). The units wheel (450) has a tab (454) that is
partially visible in FIG. 5c and fully visible in FIG. 10. The tab
(454) will engage with tens wheel gear teeth (466), shown in FIG.
10, each time the units wheel (450) makes a complete revolution,
thereby advancing the tens wheel (460) one position. The tens wheel
(460) has a scalloped edge (464) that mates with the outer edge of
the units wheel (450). This mating prevents rotation of the tens
wheel (460) except for when it is being actively engaged by the tab
(454) on the units wheel (450). This also provides an aesthetically
pleasing display, since there is no gap in the background of the
display that would otherwise be visible if both wheels (450, 460)
had a circular circumference. A slight cut-out portion (456) is
provided on the units wheel (450) to allow the tens wheel (460) to
rotate freely when the tab (454) engages with it. The tens wheel is
further provided with a paddle (462) and a missing gear tooth
(468), shown in FIG. 10, whose functions will be described in
greater detail below.
[0047] The general dose counting operation is as follows. Opening
the mouthpiece cover (301) of the device advances the uptake spool
(400) via movement of the forward pawl wheel (402). The uptake
spool (400) and displacement sensor wheel (430) are sized and
geared such that a full cycle of operation (i.e., opening the
mouthpiece cover (301) fully and closing it again), which
corresponds to a 105 degree rotation of the uptake spool (400),
will cause a 360 degree rotation of the displacement sensor wheel
(430). (This 360 degree rotation is that resulting from a full
cycle. As will be explained below, a greater rotation in fact takes
place, followed by a subsequent back-rotation to leave the net
result as a 360 degree rotation.) The complete rotation of the
displacement sensor wheel (430) causes the pin (434) to make a full
revolution during which it engages a lobe (442) of the Geneva wheel
(440) and causes the Geneva wheel (440) to step forward by an
angular displacement equal to 360 degrees divided by the number of
lobes of the Geneva wheel. As shown the Geneva wheel has 5 lobes,
thus the angular displacement is 360/5 or 72 degrees. The Geneva
wheel (440) and the units wheel (450) are sized and geared so that
the 72 degree displacement of the Geneva wheel (440) corresponds to
a 36 degree rotation of the units wheel (450) and thus advances (or
decrements) the units wheel (450) by one number. As described
above, the tab (454) on the units wheel (450) advances (or
decrements) the tens wheel (460) by one number for each complete
revolution of the units wheel (450). The tens wheel (460) is shown
in FIG. 5c with markings and respective gear teeth (466), shown in
FIG. 10, to allow a dose count for a 120-dose device, but it could
clearly be re-sized and re-marked to provide counts for 30-dose,
60-dose, 200-dose, or any other desired number of doses. As shown
the counter counts `down`, that is, it starts at the maximum number
of doses in the device, displays the number of doses remaining, and
counts down to zero, but it could equally be adjusted to count
upwards from zero to show the number of doses that had been
dispensed. As shown the tens wheel (460) has a blank space
following the `1`, so that as the counter changes from `10` to `9`
it will only display the single digit `9`. Alternatively, the
numeral `0` could be printed on the tens wheel so that the display
would change from `10` to `09`. When the device has reached `0` it
should be considered empty and discarded, but if another dose is
advanced, then the units wheel (450) will rotate from `0` to `9`,
but the tens wheel (460) will rotate so that a paddle (462) covers
the units wheel display. As shown in FIG. 10, a missing gear tooth
(468) on the tens wheel (460) will subsequently prevent the tab
(454) on the units wheel (450) from further engaging the tens wheel
(460). Thus the units wheel (450) may continue to rotate
indefinitely, but the paddle (462) will remain displayed in the
window. The paddle (462) may be colored to match the outer housing
of the device or may be colored to provide an indication that the
device is empty (e.g., red). The paddle (462) may also be marked
with indicia, such as `0`, `00`, `X` or with instructions, such as
`empty`, to provide further indication that the device is
empty.
[0048] It should be understood that the same principles could be
applied to inhalers with numerous variations to that described
above. For example, the amount of tape advanced in a full cycle of
operation need not be 105 degrees, but could instead be 90 degrees,
120 degrees, 150 degrees, or any other suitable amount of
advancement. Although shown with 5 lobes, the Geneva wheel could
have 4, 6, 10 or any suitable number of lobes, preferably with the
gearing between the Geneva wheel (440) and units wheel (450)
designed to advance the units wheel by 36 degrees per engaged lobe.
Likewise, the displacement sensor could have multiple,
equally-spaced pins and be geared such that a full cycle of
operation would advance the displacement sensor by a rotation of
360 degrees divided by the number of pins (e.g., a 2-pin
displacement sensor would rotate 180 degrees for each full cycle of
operation). As shown, the forward pawl wheel arms (404,405) and the
reverse pawl wheel arms (414, 415) engage with first and second
sets of ratchet teeth, respectively, each of which has 24 equally
spaced teeth that are aligned with the others set. Alternatively, a
single set of 24 larger ratchet teeth could span the inner hub of
the uptake spool and the forward and reverse pawl wheel arms would
engage with that single set of teeth. Alternatively, different
numbers of ratchet teeth, such as 18, 20, 30, 36, 40, 48, or any
other suitable number could be employed. Also, the number of
ratchet teeth on the two sets of ratchets may be equal or
different. In one embodiment, the number of ratchet teeth on one
set is an equal divisor of the number of ratchet teeth on the other
set (e.g., a first set with 18 teeth and a second set with 36
teeth). In one embodiment, the number of ratchet teeth is an equal
divisor of 360 (e.g., 12, 15, 18, 20, 24, 30, 36, etc.), such that
equally spaced teeth are spaced apart by an integral number of
degrees. However, the spacing of the second set of teeth is
preferably sufficiently large to allow the uptake spool (400) to
have a limited number of equally spaced closed positions of the
kind shown in FIG. 5 b, so that the resting locations of the pin
(434) straddle the changeover interval of the Geneva wheel
(440).
[0049] Further details of the interaction of the forward and
reverse pawl wheels (402, 412) with the dose counting mechanism
will be described with reference to FIGS. 5a,b,c to 9a,b,c. Several
alignment features are evident in FIGS. 5a,b,c where the inhaler is
in the mouthpiece cover closed position. The elongate carrier (100)
has some slack in it. The forward pawl wheel arms (404,405) are not
in driving engagement with any teeth on the uptake spool (400). In
particular, it can be seen that forward pawl wheel arm (404) is not
engaged with tooth (420a). The post (416) is protruding through and
engaged with the lower part of slot (417). The reverse pawl wheel
arms (414,415) are in engagement with ratchet teeth on the uptake
spool (400). In particular, it can be seen that reverse pawl wheel
arm (414) is engaged with tooth (421a). The pin (434) on the
displacement sensor wheel (430) is 180 degrees rotated away (or
directly opposed) from the Geneva wheel (440) and the units and
tens wheels (450, 460) are cooperating to display the numeral
`106`.
[0050] As the mouthpiece cover (301) is opened it rotates the cover
pivot (410). After a flat side of the cover pivot has rocked over
an inwardly-facing angled edge of the forward pawl wheel, the cover
pivot rotates the forward pawl wheel (402) thus causing the forward
pawl wheel arms (404,405) to come into engagement with the teeth on
the uptake spool (400). In particular, as can be seen in FIG. 6a,
which shows the inhaler in a position where the mouthpiece cover
has been partially opened approximately 55 degrees, the forward
pawl wheel arm (404) is now engaged with tooth (420a) and has
rotated the uptake spool (400) forward in the direction of the
arrow `A`, thus taking up the slack and advancing the elongate
carrier (100). In addition, the reverse pawl wheel (412) is rotated
by the uptake spool (400) approximately 15 degrees until the upper
(as drawn) surface of the slot (417) comes into contact with the
post (416), which prevents any further rotation of the reverse pawl
wheel (412). Further forward rotation of the uptake spool (400)
simply causes the reverse pawl wheel arms (414,415) to slip over
the teeth (421) on the inner hub of the uptake spool (400). As can
be seen in FIG. 6c, the uptake spool (400) rotation has caused a
corresponding rotation of the displacement sensor (430), but has
not yet brought the pin (434) into engagement with the Geneva wheel
(440). The numeric display remains at `106`.
[0051] As the mouthpiece cover (301) is rotated further (in this
case to approximately 75 degrees of opening) it can be seen (in
FIG. 7c) that the pin (434) on the displacement sensor (430) has
come into engagement with and partially rotated the Geneva wheel
(440), although the pin (434) is now obscured by the Geneva wheel
(440). Rotation of the Geneva wheel has caused the units wheel
(450) to partially rotate. The uptake spool (400) and elongate
carrier (100) are further advanced, but the engagement of the
forward pawl wheel arms (404,405) and the reverse pawl wheel arms
(414,415) remains as described for FIGS. 6a,b,c. The numeric
display shows the units digit partway between `6` and `5`.
[0052] As the cover is more fully opened, the pin (434) on the
displacement sensor (430) rotates past the Geneva wheel (440) after
completing the advancement of the units wheel (450) to the numeral
`5`. FIGS. 8a,b,c show the inhaler when the cover is in the fully
open position. The elongate carrier (100) has been advanced one
full dose. At this stage the pin (434) on the displacement sensor
(430) has been rotated more than 360 degrees. Upon closing of the
mouthpiece cover (301), however, the pin (434) on the displacement
sensor (430) is rotated backwards so that it reaches the same
orientation that it originally had in the cover closed position
shown in FIG. 5c. This is shown in FIG. 9c at approximately the
midpoint of the cover closing cycle. This fixed backwards rotation
is effected by the reverse pawl wheel (412) as follows. As the
cover is closed it initially rotates forward pawl wheel (402)
backwards and the uptake spool (400) is allowed to rotate slightly
backward. The backward rotation of the uptake spool (400) causes
the spool ratchet teeth (421) to engage with the reverse pawl wheel
arms (414,415). In particular, as shown in FIG. 9b, ratchet tooth
(421b) engages reverse pawl wheel arm (414). Once engaged, further
backward rotation of the uptake spool (400) by about 15 degrees
causes backward rotation of the reverse pawl wheel (412) until the
lower (as drawn) surface of the slot (417) in the reverse pawl
wheel (412) comes into contact with the fixed post (416). This
arrests motion of the reverse pawl wheel (412) and the uptake spool
(400). At this point the reverse pawl wheel (412) has reached its
original orientation as shown in FIG. 5b. Continued closing of the
mouthpiece cover continues to rotate the forward pawl wheel (402)
backwards towards its original orientation with the forward pawl
wheel arms (404,405) slipping over the spool teeth (420), since the
spool teeth are held fixed by the reverse pawl wheel (412). As
shown in FIG. 9a, the forward pawl wheel arm (404) has rotated back
a few teeth from the initial tooth (420a) that it was engaged with
as it advanced the elongate carrier (100). The uptake spool (400)
has been advanced forward 7 gear teeth corresponding to a complete
dose. When the cover is fully closed the forward pawl wheel (402)
will have returned to its original orientation as shown in FIG.
5a.
[0053] It is important to note that the position of the reverse
pawl wheel is fixed when the mouthpiece cover is closed by virtue
of one of the ratchet teeth on the uptake spool (400) pressing
against the reverse pawl wheel arms (414, 415), in one direction
and the lower surface of the slot in the reverse pawl wheel (412)
pressing against the fixed post (416) in the other direction. As
exemplified above, the uptake spool (400) has 24 ratchet teeth
(421a,b, . . . ) that are spaced at 15 degree intervals from their
neighbors and that interact with the reverse pawl wheel arms (414,
415). Thus, the reverse pawl wheel (412) will restrict the possible
positions of the uptake spool (400) to specific 15 degree
increments relative to the outer housing when the cover is closed.
As described above, the uptake spool (400) is geared to cause a 360
degree rotation of the displacement sensor wheel (430) for a 105
degree rotation of the uptake spool (400), corresponding to a full
dose advancement. 105 degree rotation of the uptake spool (400)
corresponds to 105/360.times.24 gear teeth, which is 7 gear teeth.
Since a 15 degree rotation of the uptake spool (400) corresponds to
1/7th of a full dose advancement, then it also corresponds to 1/7th
of a complete rotation of the displacement sensor wheel (430) or
about 51.4 degrees. Thus, any partial advance and reclosing of the
mouthpiece cover can only advance the displacement sensor in
increments of about 51.4 degrees.
[0054] This can be further explained with reference to FIG. 11
which shows the pin (434) on the displacement sensor (430) in its
initial position directly opposed to the Geneva wheel (440). The
phantom circles show the 6 other potential resting locations
(436a,b,c,d,e,f) for the pin (434) uniformly spaced about the
circumference of the displacement sensor (430). The lobes (442) on
the Geneva wheel (440) interact (i.e., they movably engage) with
the pin (434) on the displacement sensor (430) over a defined range
of positions. Over this range of positions the advancing motion of
the displacement sensor (430) causes an intermittent or stepwise
motion of the Geneva wheel (440) and thus the units wheel (450).
This defined range of positions may be referred to as the
changeover interval of the Geneva wheel (440). During the
changeover interval the displacement sensor is engaged with the
Geneva wheel (440) and the units wheel (450) will be in a state of
partial advancement (as in FIG. 7c). In a preferred embodiment, the
lobes (442) on the Geneva wheel (440) are shaped so that this
changeover interval is less than the distance between the resting
locations for the pin (434). During assembly of the dose counter,
it is ensured that no resting position can occur while the lobes
(442) on the Geneva wheel (440) interact with the pin (434) on the
displacement sensor (430), e.g., by positioning the pin directly
opposed from the Geneva wheel. For example, in the embodiment
described above the changeover interval is selected to be less than
51.4 degrees. In practice, this means that whenever the mouthpiece
cover is closed, the displacement sensor (430) will not be engaged
with the Geneva wheel and thus the units wheel (450) will display a
single numeral within the viewing window (320). During normal,
complete dose advancement, the pin (434) on the displacement sensor
(430) will rest directly opposed from the Geneva wheel. If a
patient advances a partial dose, then the pin (434) will come to
rest at one of the other potential resting locations
(436a,b,c,d,e,f). This enables the dose counter to retain an
accurate count of the total number of doses advanced (including any
fractional dose), but prevents the units wheel (450) from
displaying a partially advanced numeral.
[0055] For example, if the pin (434) is initially in the position
shown in FIG. 11 and the patient advances 2/7th of a dose and
recloses the cover, then the pin (434) would come to rest at the
position shown in FIG. 11 as 436b. Thus the counter would in
essence keep track that 2/7th of a dose had been advanced, but the
units wheel (450) would not have registered a change in displayed
numeral. Should the patient again advance 2/7th of a dose and
reclose the cover, then the pin (434) would now come to rest at the
position shown in FIG. 11 as 436d. The counter would now be keeping
track that a total of 4/7th of a dose had been advanced, and the
units wheel (450) would have advanced (or decremented) by one.
Should the patient now advance complete doses for the remainder of
the life of the unit, then the pin (434) would continue to come to
rest in the position shown in FIG. 11 as 436d and the units wheel
(450) would advance (or decrement) a single digit for each complete
dose advancement. It should be apparent from the above description
that any combination of partial or full dose advancements will be
accurately counted and displayed, as the counter will keep track of
partial advances and register discrete dose counts on the units
wheel.
[0056] It should be understood that it is not necessary that 24
ratchet teeth and a 5-lobe Geneva wheel be employed, but that any
other suitable combination of fixed ratchet spacings, displacement
sensor gearing, and Geneva wheel changeover interval may be
selected, as described above, to effect the same result, so long as
the distance between potential resting positions of the pin is
greater than the changeover interval of the Geneva. That is, so
long as the resting positions lie outside the changeover interval
of the Geneva.
[0057] Thus it should be clear that the general operation of the
embodiment shown in FIGS. 5a,b,c to 9a,b,c is as follows. At rest
(i.e., in the closed position, i.e., with the mouthpiece cover
closed) the elongate carrier has some slack and the displacement
sensor is in a nominal starting position that is not engaged with
the Geneva wheel. The opening motion of the mouthpiece cover causes
the uptake spool and displacement sensor to rotate until the
initial slack in the elongate carrier is taken up, at which time
the elongate carrier begins to advance. The carrier is advanced at
least a length corresponding to a dose of medicament by completely
opening the mouthpiece cover which causes further rotation of the
uptake spool which, in turn, causes the displacement sensor to make
a full revolution during advancement of the full dose. Thus, when
the device is fully open, the displacement sensor has rotated
forward by an angle greater than a full revolution (i.e., when
considering the partial rotation to take up the slack and the full
revolution to advance a dose). Closing of the mouthpiece cover
causes the displacement sensor to rotate backwards to its initial
starting point (i.e., a net rotation of 360 degrees from where it
was before the dosing cycle first started) and returns some slack
to the (advanced) elongate carrier. Thus the net motion of the
displacement sensor is one full revolution which corresponds to a
length of elongate carrier advancement equal to at least one
dose.
[0058] In more general terms, a predetermined length of advancement
of the carrier corresponding to a single dose of medicament will
cause the displacement sensor to move forward a predetermined
amount. Accurate counting and display of numerals is effected by
initially moving the displacement sensor forward by an amount
greater than the amount corresponding to the length of advancement
of the carrier and then subsequently moving the displacement sensor
backwards so that the net movement of the displacement sensor
during the combined forwards and backwards motion corresponds to
the amount of movement that corresponds to the length of
advancement of the carrier.
[0059] Although described in detail above for a particular
embodiment, a number of other variations may also be employed.
[0060] In another embodiment, shown in FIGS. 12a and 12b, the
elongate carrier (100) is shown attached to an uptake spool (500).
The uptake spool (500) may be driven forward or advanced (clockwise
as shown) by a forward pawl wheel (502) and in particular by two
forward pawl wheel arms (504,505) that engage with teeth (one of
which is denoted 520a) on the inner hub of the uptake spool (500)
that serve as ratchet teeth. The uptake spool (500) may also be
engaged by a reverse pawl wheel (512) having two reverse pawl wheel
arms (514,515) that may be better seen in the view shown in FIG.
12b. The reverse pawl wheel (512) is fixed in place with respect to
the outer housing of the device, in contrast with the embodiment
described above wherein the reverse pawl wheel (412) can undergo
limited movement with respect to the outer housing. This may be
accomplished by a number of means, for example, the reverse pawl
wheel (512) may be integrally formed with the outer housing or it
may be fixed to an internal carrier component that is in turn fixed
to the housing. The general function of the dose counter is as
described above with the exception that the reverse pawl wheel
(512) does not rotate forward on cover opening and backwards on
cover closing. The reverse pawl wheel arms (514,515) still serve to
define a fixed position for the uptake spool (500) when the
mouthpiece cover is closed, which in turn causes the displacement
sensor (not shown) to rest in one of several fixed positions, which
prevents the units wheel (450) from displaying a partially advanced
numeral.
[0061] In another embodiment (not shown), the reverse pawl wheel
could be omitted from the previous embodiments, while retaining all
of the other components (e.g., Geneva wheel, displacement sensor,
etc.). The forward pawl wheel would continue to translate
mouthpiece cover rotation into uptake spool rotation during the
mouthpiece cover opening. Upon mouthpiece cover closing, the
forward pawl wheel arms would slip past the teeth on the uptake
spool. A friction brake or other suitable means could be included
in the device to prevent backwards rotation of the uptake spool
that might otherwise be caused by the friction of the forward pawl
wheel arm sliding over the teeth as the mouthpiece cover closed.
This embodiment with a means to prevent backwards rotation would
accurately count and display tape advancement.
[0062] In another embodiment (not shown), the functions of the
Geneva wheel (440) and the units wheel (450) are integrated into a
single part. This is accomplished by replacing the gear teeth (452)
shown in FIG. 10 on the reverse side of the units wheel (450) with
ten Geneva-type lobes. Thus each time the pin (434) on the
displacement sensor (430) makes a full revolution it engages a lobe
and advances the units wheel (450) one-tenth of a rotation. In
essence, the front portion of the integrated part is a units dose
display wheel and the back portion is a ten-lobe Geneva wheel.
[0063] In another embodiment (not shown), the function of the
displacement sensor (430) and the uptake spool are integrated into
a single part. For example, the mouthpiece cover rotation angle and
the uptake spool size are adjusted, and optionally gears
introduced, so that the uptake spool makes a complete rotation for
each dose advancement. A pin is placed on the uptake spool to
directly engage with the Geneva wheel (440). Other variations would
have the uptake spool rotation angle corresponding to a full dose
divide equally into 360 degrees, e.g., 180, 120, or 90 degrees of
rotation, in which case the uptake spool would have 2, 3, or 4
pins, respectively, so that a pin would advance the Geneva wheel
whenever a full dose was advanced.
[0064] In another embodiment, the tape could be advanced by the
patient twisting a knob, pulling a handle, or pressing a button to
advance the tape.
[0065] In another embodiment, the pawl arms and the ratchet teeth
could be located on the opposite components compared to those that
have been described in the embodiments above. That is, the pawl
arms may be placed on the inner hub of the uptake spool and point
inwards. Corresponding ratchet teeth would then be located on the
central hub as part of the cover pivot. In particular, the reverse
pawl wheel arms can be integrally formed with the uptake spool and
corresponding ratchet teeth could be formed on the outer diameter
of the cover pivot.
[0066] In one aspect, a predetermined net advancement of the
advancement mechanism corresponds to an advancement of the elongate
carrier that provides sufficient length to contain a predetermined
quantity in the chamber for dispensing. (The predetermined quantity
may be a dose, or the dose may comprise a multiple of predetermined
quantities if that is what a patient is prescribed to take on each
occasion. However, generally the term `dose` is understood to
correspond to a single amount dispensed from a dry powder
inhalation device.)
[0067] The aforementioned net advancement of the advancement
mechanism causes the displacement sensor to move forward a
predetermined amount. While the particular gearing may affect the
actual distance moved, corresponding movement of these two
components enables the displacement sensor to record the net
advancement in terms of doses. Accurate counting and display of
numerals is effected by initially moving the displacement sensor
forward by an amount greater than that corresponding to the
predetermined net advancement of the advancement mechanism and then
subsequently moving the displacement sensor backwards so that the
net movement of the displacement sensor during the combined
forwards and backwards motion, which corresponds to the net
movement of the advancement mechanism, also corresponds to at least
the predetermined quantity of medicament, and the net movement of
the advancement mechanism is the same for each such dispensing
operation.
[0068] When the advancement mechanism is reset, e.g., as a result
of closing a mouthpiece cover, the initial part of the resetting
causes the displacement sensor to rest in rotationally symmetrical
positions relative to the housing (and other parts fixedly engaged
with the housing) for every such resetting. Thus, due to these
precise positions and the precise gearing between the advancement
mechanism and the displacement sensor, the resting location for the
displacement sensor is always one of a prescribed number of
rotationally symmetrical positions of the displacement sensor.
[0069] In dry powder inhalation devices that wind an elongate
carrier onto an uptake spool and wherein a dispensing operation
comprises turning the spool through a fixed angle, the length wound
per dispensing operation may increase as the amount on the uptake
spool increases. In certain dry powder inhalation devices of the
description, the variation in length wound is kept to a minimum by
not allowing the winding diameter to increase much throughout the
length of advanced elongate carrier. This is achieved by making the
winding diameter at the start large in comparison with the
thickness of elongate carrier, and dispenses with the need for a
compensation mechanism to equalize the length wound per advancement
throughout the length of the elongate carrier. The length wound
onto the uptake spool increases from marginally in excess of the
predetermined length at the start of the elongate carrier to
marginally more in excess at the end of the elongate carrier.
[0070] This, along with having a fixed dosing length within the
chamber, allows a fixed angle of rotation of the uptake spool (i.e.
fixed extent of advancement of the advancement mechanism) to
correspond accurately to dispensed doses, and therefore allows the
dose counter having movement coordinated therewith to display the
number of dispensed doses accurately.
[0071] In one embodiment, the description provides a method of
dispensing a predetermined quantity of medicament from a dry powder
inhalation device. The device comprises a housing defining a
chamber, a patient port in communication with said chamber, an
elongate carrier carrying medicament, and an advancement mechanism
for advancing a length of the elongated carrier into the
chamber.
[0072] The method comprises moving a length of the elongate carrier
forwards into the chamber, the length corresponding to the
predetermined quantity of medicament. A length of the elongated
carrier is moved forwards with the advancement mechanism, the
length corresponding to greater than that needed to provide the
predetermined quantity of medicament. Subsequently, the advancement
mechanism is moved backwards so that the net length of the elongate
carrier moved forwards with the advancement mechanism corresponds
to at least the predetermined quantity of medicament and the net
movement of the advancement mechanism is the same for each
dispensing operation. Medicament is then dispensed from the
elongate carrier within the chamber, in such a way that a patient
can inhale it through the patient port.
[0073] The method may further comprise a method for counting the
predetermined quantity of medicament dispensed per dispensing
operation. The dry powder inhalation device further comprises a
displacement sensor that moves in association with movement of the
elongate carrier by the advancement mechanism and a units counter
to record a single count for each dispensing operation. The method
further comprises converting the net length of the elongate carrier
moved by the advancement mechanism, via the displacement sensor,
into an advancement of the units counter by one unit.
[0074] It is to be understood that where a first component moves in
association with a second component, it is meant that any motion of
the first is coincident with motion of the second, and that neither
can move independently of the other; although the extent of motion
may be different e.g., due to gearing.
[0075] In another embodiment, the description provides a method of
advancing and counting doses in a dry powder inhaler, the dry
powder inhaler comprising an elongate carrier carrying medicament,
a displacement sensor that moves in association with movement of
the elongate carrier by the advancement mechanism, and a units dose
counter that moves with movement of the displacement sensor.
Advancement of the elongate carrier by a length corresponding to a
single dose of medicament will cause the displacement sensor to
move forward a predetermined amount. The method comprises the steps
of (i) advancing a length of the elongate carrier carrying
medicament, wherein the length corresponds to a dose of medicament;
(ii) moving the displacement sensor forward with movement of the
elongate carrier by the advancement mechanism, wherein the
displacement sensor is moved forward by an amount greater than the
predetermined amount corresponding to the length of advancement of
the elongate carrier; (iii) converting the forward movement of the
displacement sensor into advancement of the units dose counter by
one unit; and (iv) subsequently moving the displacement sensor
backwards so that the net movement of the displacement sensor
during the forwards and backwards motion corresponds to the
predetermined amount of movement of the advancement mechanism that
corresponds to the length of advancement of the carrier.
* * * * *