Patent Application
20100050770
The present invention is generally directed to the manufacturing of sealed containers equipped with valves, such as those employed in metered dose delivery units.
Metered Dose Inhalers or MDIs are employed as a means of delivering medicaments to patients in need thereof via aerosol administration. More specifically, pharmaceutical formulations are delivered to the patient which contain one or more medicaments and a propellant.
A typical MDI includes, among other components, a can or canister that houses the formulation therein. A significant factor is ensuring that the formulation is sufficiently mixed during patient use to allow for as uniform and consistent dosing as possible. During can testing, it is therefore important to understand as best as possible the level of mixing the formulation in the can is experiencing. Data collection is made in an attempt to quantify the actual motion or acceleration of the can. It is highly desirable that any tests or QC measurements be done under consistent conditions, including the Initial and subsequent shaking steps of the can. Many of the products have the potential to be very sensitive to even small changes in shaking. Being able to quantify the similarity of shakes from one test/test batch to the next helps reduce (through training) or quantify (through recording) the Inherent error of experimental setup and operator induced variation.
One method of carrying out acceleration measurements on the can is to place a wired accelerometer in a similar sized can, then run the wire to an electronic apparatus to record the results. Notwithstanding any advantages of this technique, such a method has a perceived shortcoming in that it is difficult, if not impossible to run the device through a machine as a normal can, due to the wire. Thus, the machine must be stopped, device inserted, then restart the machine. This may lead to inaccurate measurements since machine is not running in continuous, steady state mode. Additionally, the wire has the capability of preventing or substantially impeding the ability of people to shake the device as they would a normal can, either chaining the shake to work around the cable, or the cable actually slowing down the shake. Also, the wired version is subject to possible damage.
There is a need in the art to address the problems noted above.
In one aspect, the invention comprises an apparatus comprising a main body member; and a transducer in communication with the main body member, the transducer adapted to receive an acceleration force imparted to the main body member.
In another aspect, the invention provides a method for assessing acceleration forces imparted to an apparatus. The method comprises applying an external acceleration force to an apparatus, the apparatus comprising a main body member and a transducer in communication with the main body member, the transducer adapted to receive the external acceleration force imparted to the main body member, wherein the transducer converts the acceleration forces to electrical signals and the acceleration forces are accessed.
These and other aspects are provided by the invention.
a is a perspective exploded view of a battery charger for use in accordance with the present invention;
b is a diagram illustrating the battery charger set forth in
The invention will now be described with respect to the embodiments set forth herein. It should be appreciated that these embodiments are set forth to illustrate the invention, and that the invention is not limited to these embodiments. Such embodiments may or may not be practiced mutually exclusive of each other.
All publications, patents, and patent applications cited herein, whether supra or Infra, are hereby incorporated herein by reference in their entirety to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.
It must be noted that, as used in the specification and appended claims, the singular forms “a”, “an” “the” and “one” include plural referents unless the content clearly dictates otherwise.
Medicaments that may be employed in MDIs set forth herein include a variety of pharmaceutically active ingredients, such as, for example, those which are useful in inhalation therapy. In general, the term “medicament” is to be broadly construed and include, without limitation, actives, drugs and bioactive agents, as well as biopharmaceuticals. In various embodiments, medicament may be present in micronized form. Appropriate medicaments may thus be selected from, for example, analgesics, (e.g., codeine, dihydromorphine, ergotamine, fentanyl or morphine); anginal preparations, (e.g., diltiazem; antiallergics, e.g., cromoglicate, ketotifen or nedocromil); antiinfectives (e.g., cephalosporins, penicillins, streptomycin, sulphonamides, tetracyclines and pentamidine); antihistamines, (e.g., methapyrilene); anti-inflammatories, (e.g., beclometasone dipropionate, fluticasone propionate, flunisolide, budesonide, rofleponide, mometasone furoate, ciclesonide, triamcinolone acetonide or 6α, 9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxy-androsta-1,4-diene-17β-carbothioic acid S-(2-oxo-tetrahydro-furan-3-yl) ester)); antitussives, (e.g., noscapine; bronchodilators, e.g., albuterol (e.g. as sulphate), salmeterol (e.g. as xinafoate), ephedrine, adrenaline, fenoterol (e.g as hydrobromide), formoterol (e.g., as fumarate), isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol (e.g., as acetate), reproterol (e.g., as hydrochloride), rimiterol, terbutaline (e.g., as sulphate), isoetharine, tulobuterol, 4-hydroxy-7-[2-[[2-[[3-(2-(henylethoxy)propyl]sulfonyl]ethyl]-amino]ethyl-2(3H)-benzothiazolone), 3-(4-{[6-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}amino) hexyl]oxy}butyl) benzenesulfonamide, 3-(3-{[7-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}amino)heptyl]oxy}propyl)benzenesulfonamide, 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol; diuretics, (e.g., amiloride; anticholinergics, e.g., ipratropium (e.g., as bromide), tiotropium, atropine or oxitropium); hormones, (e.g., cortisone, hydrocortisone or prednisolone); xanthines, (e.g., aminophylline, choline theophyllinate, lysine theophyllinate or theophylline); therapeutic proteins and peptides, (e.g., insulin). It will be clear to a person skilled in the art that, where appropriate, the medicaments may be used in the form of salts, (e.g., as alkali metal or amine salts or as acid addition salts) or as esters (e.g., lower alkyl esters) or as solvates (e.g., hydrates) to optimise the activity and/or stability of the medicament. It will be further clear to a person skilled in the art that where appropriate, the medicaments may be used in the form of a pure isomer, for example, R-salbutamol or RR-formoterol.
Particular medicaments for administration using pharmaceutical formulations in accordance with the invention include anti-allergics, bronchodilators, beta agonists (e.g., long-acting beta agonists), and anti-inflammatory steroids of use in the treatment of respiratory conditions as defined herein by inhalation therapy, for example cromoglicate (e.g. as the sodium salt), salbutamol (e.g. as the free base or the sulphate salt), salmeterol (e.g. as the xinafoate salt), bitolterol, formoterol (e.g. as the fumarate salt), terbutaline (e.g. as the sulphate salt), reproterol (e.g. as the hydrochloride salt), a beclometasone ester (e.g. the dipropionate), a fluticasone ester (e.g. the propionate), a mometasone ester (e.g., the furoate), budesonide, dexamethasone, flunisolide, triamcinolone, tripredane, (22R)-6α,9α-difluoro-11β,21-dihydroxy-16α, 17α-propylmethylenedioxy-4-pregnen-3,20-dione. Exemplary long-acting beta agonists include, without limitation, salmeterol (e.g. as xinafoate), 3-(4-{[6-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}amino)hexyl]oxy}butyl) benzenesulfonamide, 3-(3-{[7-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl) phenyl]ethyl}amino)heptyl]oxy}propyl) benzenesulfonamide, 4-{(1R)-2-[(6-{2-[(2,6-dichlorobenzyl)oxy]ethoxy}hexyl)amino]-1-hydroxyethyl}-2-(hydroxymethyl)phenol, 2-hydroxy-5-((1R)-1-hydroxy-2-{[2-(4-{[(2R)-2-hydroxy-2-phenylethyl]amino}phenyl)ethyl]amino}ethyl)phenylformamide, and 8-hydroxy-5-{(1R)-1-hydroxy-2-[(2-{4-[(6-methoxy-1,1′-biphenyl-3-yl)amino]phenyl}ethyl)amino]ethyl}quinolin-2(1H)-one. Exemplary anti-inflammatory steroids include, without limitation, fluticasone propionate, (6α,11β,16α,17α)-6,9-difluoro-17-{[(fluoromethyl)thio]carbonyl}-11-hydroxy-16-methyl-3-oxoandrosta-1,4-dien-17-yl 2-furoate, and (6α,11β,16α,17α)-6,9-difluoro-17-{[(fluoromethyl)thio]carbonyl}-11-hydroxy-16-methyl-3-oxoandrosta-1,4-dien-17-yl 4-methyl-1,3-thiazole-5-carboxylate.
Medicaments useful in erectile dysfunction treatment (e.g., PDE-V Inhibitors such as vardenafil hydrochloride, along with alprostadil and sildenafil citrate) may also be employed. It should be understood that the medicaments that may be used in conjunction with the inhaler are not limited to those described herein.
Salmeterol, especially salmeterol xinafoate, salbutamol, fluticasone propionate, beclomethasone dipropionate and physiologically acceptable salts and solvates thereof are especially preferred.
It will be appreciated by those skilled in the art that the formulations according to the invention may, if desired, contain a combination of two or more medicaments. Formulations containing two active ingredients are known for the treatment of respiratory disorders such as asthma, for example, formoterol (e.g. as the fumarate) and budesonide, salmeterol (e.g. as the xinafoate salt) and fluticasone (e.g. as the propionate ester), salbutamol (e.g. as free base or sulphate salt) and beclometasone (as the dipropionate ester) are preferred.
In one embodiment, a particular combination that may be employed is a combination of a beta agonist (e.g., a long-acting beta agonist) and an anti-inflammatory steroid. One embodiment encompasses a combination of fluticasone propionate and salmeterol, or a salt thereof (particularly the xinafoate salt). The ratio of salmeterol to fluticasone propionate in the formulations according to the present invention is preferably within the range 4:1 to 1:20. The two drugs may be administered in various manners, simultaneously, sequentially, or separately, in the same or different ratios. In various embodiments, each metered dose or actuation of the inhaler will typically contain from 25 μg to 100 μg of salmeterol and from 25 μg to 500 μg of fluticasone propionate. The pharmaceutical formulation may be administered as a formulation according to various occurrences per day. In one embodiment, the pharmaceutical formulation is administered twice daily.
Referring now to
As shown in
Referring to the partially cutaway view of valve assembly 14 in
Referring to
One embodiment of transducer 120 is illustrated in
An embodiment of the circuit card 300 employed in accordance with the invention will now be described in detail in
In one embodiment, the power section 310 is built up from a 1.2 volt rechargeable battery 160, a DC-DC step-up converter and the associated discrete components for control and filtering, the selection of which is known in the art. In addition, the circuit is kept at one end of the board on one side of the board to minimize electrical noise and EMI and attempt to keep the sensitive signal integrity. The DC-DC converter was tuned to supply 5 VDC with minimal switching noise transmitted to the 5 volt bus on the circuit card 300. Other components may be employed to form the power section without deviating from the scope of the invention.
In one embodiment, the processor section (e.g., microprocessor) 320 is positioned in the vicinity of the center of the circuit card between the power section and transducer. In such an embodiment, the processor also has a separate “clean” supply that employs a discrete inductor and capacitor to filter out the high frequency switching noise of the power supply.
In one embodiment, the transducer section includes the Analog Devices 2-Axis accelerometer and a number of discrete resistors and capacitors that are used to adjust the timing, output and sensitivity of the transducer. In addition, in one embodiment, the circuit card has a separate ground layer under the transducer that helps to isolate any power supply noise from the supply so the transducer can supply the microprocessor with a clean signal.
The system architecture, component layout and circuit card configuration all work together to provide a compact power system that can supply adequate power while minimizing compromising signal integrity from the acceleration transducer.
Additional components of the apparatus 100 are illustrated in
Optionally, battery 160 may be rechargeable. As an example, in one embodiment, upon removal of data module 190, a charger may be inserted into opening 230 which functions to recharge battery 160. One example of a charger is set forth in
In general, the apparatus includes electronic circuitry, including, as an example those components known in the art, which communicates with the transducer 120 and is adapted to receive an electrical output signal produced by the transducer 120. The electrical signal is indicative of a magnitude of the acceleration force imparted to the main body member. In one embodiment, the electronic circuitry may be disposed within a housing of the apparatus. Alternatively, in another embodiment, the electronic circuitry may be disposed remotely in relation to a housing of the apparatus. In such an embodiment, as an example, the circuitry can communicate with the transducer via wireless communication (e.g., BlueTooth or IR Communication links). Alternatively, the circuitry can communicate with the transducer through an electrical conduit.
As disclosed above, the electrical circuitry may be disposed within a housing of the apparatus. In one embodiment, as an example, the electronic circuitry is present in a data module 190 which is capable of processing the output signal produced by the transducer 120. In the embodiment illustrated in
More specifically, in one embodiment and as an example, the insertion of data module 190 in opening in cylindrical shell 220 and its contact with a support plate serves to power ON battery 160, thus allowing data module 190 to communicate with transducer 120 via circuit card 300. Upon completion of the acceleration data gathering session, data module 190 may be removed from a support plate which serves to turn the battery 160 OFF. As desired by the end user, data module 190 may then be placed in communication with an additional electronic device(s) (not shown) for any number of operations such as, for example, data processing, storage, and/or display. As an example, data module 190 may be inserted in a computer.
In accordance with the present invention, the apparatus may include at least one electrical contact accessible from outside the housing. The electrical contact may be employed in a manner known in the art. The electrical contact may be adapted to enable communication between the electronic circuitry and an external computer device disposed remotely in relation to the housing. This embodiment is generally depicted in
In a particular embodiment, the apparatus may further include a mode switch electrically communicating with the electronic circuitry and accessible from outside of the housing. Advantageously, the mode switch is alternatively switchable to a record mode of the apparatus, wherein electrical communication is established between the transducer and the electronic circuitry in the record mode, and electrical communication is established between the electronic circuitry and the external computer device in the communicate mode.
In one embodiment, the mode switch may be mounted to the apparatus. The mode switch may be mounted in various manners, the selection of which is known to one skilled in the art. For example, in one embodiment, the mode switch may be adapted so as to be mounted in a cradle, wherein the cradle includes the mode switch. The cradle may include a contact adapted for electrical communication with the apparatus to provide power to the apparatus in a manner known to one skilled in the art.
As one possible embodiment of the mode switch, a RECORD/COMMUNICATE switch could be mounted in the base of the cradle. In this configuration, the mounting of the apparatus of the invention into the cradle may be capable of automatically switching the apparatus to the COMMUNICATE mode, and the removal of the apparatus from the cradle can automatically switch the apparatus to the RECORD mode. As a further alternative, a suitable electrical contact element can be added to the cradle to supply low voltage power to the apparatus while the apparatus is communicating through the cradle, thereby conserving battery life. The modifications required to implement these alternative embodiments should be understood by persons skilled in the art. Such modifications may include the addition of one or more contact pads to the base of the apparatus.
In one embodiment, referring to
In another aspect, the invention encompasses a method for accessing acceleration forces imparted to an apparatus. The method includes applying an external acceleration force to an apparatus. The apparatus includes a main body member and a transducer in communication with the main body member. The transducer is adapted to receive the external acceleration force imparted to the main body member. The transducer converts the acceleration forces to electrical signals and the acceleration forces are accessed. Such forces may be accessed by employing electrical data gathering and processing devices and techniques including, without limitation, those described herein.
The step of applying an external force to an apparatus may be carried out by various manners, as illustrated in
It will be understood that various details of the invention may be changed without departing from the scope of the invention. Furthermore, the foregoing description is for the purpose of illustration only, and not for the purpose of limitation—the invention being defined by the claims.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/US2006/000446 | 1/6/2006 | WO | 00 | 11/20/2009 |
| Number | Date | Country | |
|---|---|---|---|
| 60642584 | Jan 2005 | US |
