Patent Application
20200001026
Patients with respiratory disorders, such as asthma and COPD, are commonly prescribed medicaments that are self-administered via the use of inhaler devices such as, for example, metered-dose inhalers (MDIs) and soft mist inhalers (SMI). Inhalers generate a cloud of aerosolized medicament which a patient inhales through their mouth in order to deliver the medication to their airways and lungs. Often, a patient will improperly use an inhaler which can cause improper dosing of the medicament.
One way to reduce improper use of an inhaler is through the use of an add-on device, such as a spacer. A spacer is a device that is paired with an inhaler such that the spacer suspends the aerosolized medicament within the spacer chamber, allowing the patient to inhale the full dose of the medicament with one or more deep breaths. However, even with the availability of a spacer, many patients have difficulty managing their respiratory disorder for several reasons, including inconsistent, under, or over utilization of the medicament, ineffective inhaler technique, and/or infrequent assessment of and feedback of their lung health.
Some spacers include patient technique coaching via mechanical means such as a whistle for when the patient inhales too rapidly. However, these mechanical means do not generate longitudinal trends nor do they provide information on patient inhalation volume or duration.
One way patient's test their lung function and, thus, assess their lung function is by a spirometer. A spirometer is a separate device from the inhaler, where the patient can measure their inhalation volume or duration. Spirometers have the disadvantage in that the patient would have to carry the spirometer separately from the spacer. Further, the spirometer cannot be chronologically associated with patient inhaler technique or medicament utilization.
Therefore, it would be beneficial to provide a smart spacer that measures and records a patient's inhaled airflow and exhaled airflow. It would also be beneficial to provide a smart spacer that can generate metrics on inhalation technique, record medicament utilization and generate metrics on lung health so that a practitioner monitoring a patient's respiratory disorder can track a patient's improvement. Further, it would be beneficial to provide a smart spacer that offers a spirometry feature.
The present application provides a smart spacer that measures and records a patient's inhaled airflow and exhaled airflow. The smart spacer also generates in real time metrics on inhalation technique, records medicament utilization and generates metrics on lung health in real time so that a patient can track their own improvement, as well as, a practitioner monitoring a patient's respiratory disorder can track said patient's improvement. Further, these metrics can be displayed on the patient's phone, the practitioner's computer or other display. The smart spacer provides a mode for initiating a spirometry feature that can be transmitted to the patient's phone and transmitted to the practitioner to monitor patient therapy and adjust the dose of the aerosolized medicament being administered to the patient.
In one embodiment, a spacer is provided. The spacer comprises a chamber having an interior surface and an exterior surface. The interior surface of the chamber is configured to receive aerosolized medicament from an inhaler and has at least one sensor for measuring airflow in the chamber. The spacer includes an actuator that is disposed on the exterior surface of the chamber that is configured to initiate measurement of airflow in the chamber.
In another embodiment, a spacer is provided. The spacer comprises a chamber having an interior surface and an exterior surface. The interior surface of the chamber is configured to receive inhalation air and exhalation air from a patient. The interior surface has at least one sensor for measuring airflow in the chamber. The spacer includes an actuator that is disposed on the exterior surface of the chamber that is configured to initiate measurement of airflow in the chamber.
In yet another embodiment, a method of making a spacer is provided. The method comprises providing a spacer comprising a chamber having an interior surface, an exterior surface, and a proximal opening and a distal opening opposite the proximal opening, the interior surface of the chamber configured to receive inhalation air and exhalation air from a patient, attaching to the interior surface of the chamber at least one sensor for measuring airflow in the chamber; and attaching an actuator on the exterior surface of the chamber, the actuator configured to initiate measurement of airflow in the chamber.
In one embodiment, a method of using a spacer is provided. The method comprises attaching an inhaler to a distal end opening of the spacer, the spacer comprising a chamber having an interior surface and an exterior surface, the interior surface of the chamber configured to receive aerosolized medicament from an inhaler and having at least one sensor for measuring airflow in the chamber; and an actuator disposed on the exterior surface of the chamber configured to initiate measurement of airflow in the chamber.
In some embodiments, a method of using a spacer is provided. The method comprises removing an inhaler from a distal end opening of the spacer, the spacer having a chamber having an interior surface and an exterior surface, the interior surface of the chamber configured to receive inhalation air and exhalation air from a patient, the interior surface having at least one sensor for measuring airflow in the chamber; and an actuator disposed on the exterior surface of the chamber configured to initiate measurement of airflow in the chamber.
Other features and advantages of the present disclosure will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating preferred embodiments of the disclosure, are given by way of illustration only, since various changes and modifications within the spirit and scope of the disclosure will become apparent to those skilled in the art from this detailed description.
In part, other aspects, features, benefits and advantages of the embodiments will be apparent with regard to the following description, appended claims, and accompanying drawings in which:
It is to be understood that the figures are not drawn to scale. Further, the relation between objects in a figure may not be to scale, and may in fact have a reverse relationship as to size. The figures are intended to bring understanding and clarity to the structure of each object shown, and thus, some features may be exaggerated in order to illustrate a specific feature of a structure.
The present disclosure may be understood more readily by reference to the following detailed description of the disclosure presented in connection with the accompanying drawings, which together form a part of this disclosure. It is to be understood that this disclosure is not limited to the specific devices, methods, conditions or parameters described and/or shown herein, and that the terminology used herein is for the purpose of describing particular embodiments by way of example only and is not intended to be limiting of the claimed disclosure. The following description is presented to enable any person skilled in the art to make and use the present disclosure.
Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the application are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. Moreover, all ranges disclosed herein are to be understood to encompass any and all subranges subsumed therein. For example, a range of “1 to 10” includes any and all subranges between (and including) the minimum value of 1 and the maximum value of 10, that is, any and all subranges having a minimum value of equal to or greater than 1 and a maximum value of equal to or less than 10, e.g., 5.5 to 10.
As used in the specification and including the appended claims, the singular forms “a,” “an,” and “the” include the plural, and reference to a particular numerical value includes at least that particular value, unless the context clearly dictates otherwise.
Ranges may be expressed herein as from “about” or “approximately” one particular value and/or to “about” or “approximately” another particular value. When such a range is expressed, another embodiment includes from the one particular value and/or to the other particular value.
Spatially relative terms such as “under”, “below”, “lower”, “over”, “upper”, and the like, are used for ease of description to explain the positioning of one element relative to a second element. These terms are intended to encompass different orientations of the device in addition to different orientations than those depicted in the figures. Further, terms such as “first”, “second”, or the like, are also used to describe various elements, regions, sections, etc. and are also not intended to be limiting. Like terms refer to like elements throughout the description.
As used herein, the terms “having”, “containing”, “including”, “comprising” and the like are open ended terms that indicate the presence of stated elements or features, but do not preclude additional elements or features.
The term “spacer” refers to a device used to increase the ease of administering aerosolized medication from an inhaler to a patient. A spacer adds space in the form of a tube or chamber between the mouth and canister of medication. A spacer assists a patient to breathe deeply, as well as assist patients that are unable to synchronize their breathing so that they inhale just as the inhaler is actuated.
The term “spirometer” refers to a device for measuring the volume of air inspired and expired by the lungs. A spirometer measures ventilation, the movement of air into and out of the lungs.
The term “metered dose inhaler” (MDI) refers to a device that delivers a specific amount of medicament to the lungs in the form of a short burst of aerosolized medicament that is usually self-administered by the patient via inhalation.
The term “soft mist inhaler (SMI)” can include a multidose, propellant-free, hand-held liquid inhaler that represents a category of inhaler devices. “Soft Mist” is used to describe the mechanism of aerosol generation and the qualities of the aerosol cloud. An example of a SMI is Respimat® (Boehringer Ingelheim, Ingelheim am Rhein, Germany).
The term “medicament” includes a substance suitable for oral or nasal inhalation. The medicament can include at least one active pharmaceutical ingredient and an excipient.
The term “pharmaceutically acceptable salt” or “salt” comprises inorganic and organic salts. Examples of organic salts may include formate, acetate, trifluoroacetate, propionate, butyrate, lactate, citrate, tartrate, malate, maleate, succinate, methanesulfonate, benzenesulfonate, xinafoate, pamoate, and benzoate. Examples of inorganic salts may include fluoride chloride, bromide, iodide, phosphate, nitrate and sulfate.
As used herein, the term “medicament” and “active pharmaceutical ingredient” (API) as used herein, are interchangeable terms and include any substance (i.e., compound or composition of matter) which, when administered to an organism (human or animal) induces a desired pharmacologic and/or physiologic effect by local and/or systemic action. The term therefore encompasses substances traditionally regarded as actives, drugs or bioactive agents, as well as biopharmaceuticals typically employed to treat a number of conditions which is defined broadly to encompass diseases, disorders, infections, or the like. Exemplary medicaments (APIs) include, without limitation, antibiotics, antivirals, H2-receptor antagonists, 5HT1 agonists, 5HT3 antagonists, COX2-inhibitors, steroids (e.g., prednisone, prednisolone, dexamethasone), non-steroidal anti-inflammatory medicaments (APIs), muscarinic M3 receptor agonists or anticholinergic agents, β2-adrenoceptor agonists, compounds having a dual muscarinic antagonist and β2-agonist activity and glucocorticoid receptor agonists.
In some embodiments, the medicament (API) is ipratropium, tiotropium, oxitropium, trospium, aclidiniums, perenzepine, telenzepine, ephedrine, adrenaline, isoprenaline, metaproterenol, phenylephrine, phenylpropanolamine, pirbuterol, reproterol, rimiterol, isoetharine, carmoterol, albuterol, terbutaline, bambuterol, fenoterol, salbutamol, tulobuterol formoterol, salmeterol, prednisone, prednisolone, flunisolide, triamcinolone acetonide, beclomethasone, budesonide, fluticasone, ciclesonide, mometasone as well as salts and/or solvates thereof. In some embodiments, the medicament (API) is glycopyrronium bromide, formoterol fumarate, tiotropium bromide In some embodiments, the medicament (API) is a glucocorticosteroid, such as, for example, fluticasone, budesonide, mometasone or ciclesonide.
The term “excipient” is used to describe an ingredient other than the active pharmaceutical ingredients. The selection of an excipient can depend on factors such as the particular mode of administration, the effect of the excipient on solubility and stability, and the nature of the dosage form.
The term “aerosolized medicament” refers to a particulate and/or liquid medicament that is converted into a fine spray or colloidal suspension in air. Aerosolized medicament can be administered to a patient via inhaler devices such as, for example, MDIs or SMIs.
The headings below are not meant to limit the disclosure in any way; embodiments under any one heading may be used in conjunction with embodiments under any other heading.
Reference will now be made in detail to certain embodiments of the invention, examples of which are illustrated in the accompanying drawings. While the invention will be described in conjunction with the illustrated embodiments, it will be understood that they are not intended to limit the invention to those embodiments.
A smart spacer 20, as shown in
The smart spacer includes a chamber 22. The chamber is configured to receive and hold an aerosolized medicament 24 dispensed from an inhaler 26, such as a metered-dose inhaler (MDI) or a soft mist inhaler (SMI) within an interior surface 28. The chamber is also configured to receive inhaled air and exhaled air from a patient, as described herein.
In some embodiments, the chamber has dimensions of about 10 to about 20 centimeters (cm) in length and about 3 to about 8 cm in width. In some embodiments, the chamber has a length of about 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 to about 20 cm. In some embodiments, the chamber has a width of about 3, 4, 5, 6, 7 to about 8 cm.
The chamber includes a proximal end opening 30, a distal end opening 32 and a longitudinal axis AA disposed therebetween. The proximal end opening of the chamber includes a mouthpiece 34 or a mask 35 and is configured for engagement with the mouth of the patient P. The mouthpiece is in alignment with the proximal and distal end openings. In some embodiments, the mouthpiece is detachable. The distal end opening is configured for engagement with a portion of the inhaler, such as the mouthpiece 36 of the inhaler, as shown in
In some embodiments, a diameter of the distal end opening is the same or greater than a diameter of the mouthpiece of the inhaler. In some embodiments, the distal end opening has a diameter of about 0.5 cm to about 2 cm and the mouthpiece of the inhaler has a diameter that is about 0.5 cm to about 1.5 cm. In some embodiments, the distal end opening has a length that is the same or greater than a length of the mouthpiece of the inhaler. In some embodiments, the distal end opening has a length of about 1 to about 3 cm and the mouthpiece of the inhaler has a length of about 1 to about 2.5 cm.
In some embodiments, the chamber is devoid of any valve or any one-way valves. In some embodiments, a valve may interfere with medicament delivery to the patient and/or airflow.
The interior surface of the chamber includes at least one sensor 38 for measuring airflow in the chamber. For example, the at least one sensor measures volumetric inhalation airflow and volumetric exhalation airflow of the patient. The at least one sensor is disposed adjacent to the proximal end opening, as shown in
In some embodiments, the at least one sensor can be paired with at least one sensor that measures temperature and barometric pressure to assist in measuring the volumetric inhalation airflow and volumetric exhalation airflow of the patient. In some embodiments, the at least one sensor can be paired with at least one sensor that includes an image sensor, a photodetector sensor, a color detector sensor, a pressure sensor, a temperature sensor, and/or a humidity sensor.
In some embodiments, the at least one sensor comprises a first sensor 38 and a second sensor 38, as shown in
In some embodiments, the at least one sensor can be detachable. In some embodiments, the at least one sensor can be attached to the interior surface of the chamber via adhesive, adhesive strips, Velcro®, clips, hooks, magnets, snaps, buttons, interference fittings, friction fittings, compressive fittings, posts, connectors, and/or fixation plates. In some embodiments, the at least one sensor can be friction fit or snap fit into a recess or an indent 39 located on the interior surface of the chamber, as shown in
In some embodiments, the at least one sensor can be covered by a mesh, such as a hydrophobic mesh such that the one or more sensors are made waterproof. In other embodiments, the at least one sensor can be covered by a plastic sleeve that creates a waterproof environment for the at least one sensor. The at least one sensor can also be coated by hydrophobic films. This will aid in preventing or reducing damage when the spacer and/or the at least one sensor is washed.
The spacer includes an actuator 42 disposed on an exterior surface 44 of the chamber that is configured to initiate measurement of airflow in the chamber. The actuator functions to initiate or turn on the spacer. In some embodiments, the actuator can be a button. The actuator can be disposed anywhere on the exterior surface of the chamber which is easy for the patient to touch. For example, the actuator can be disposed on the exterior surface adjacent to the distal end opening or on a top portion of the exterior surface. In some embodiments, the actuator can be disposed adjacent to the proximal end opening. In some embodiments, the actuator is detachable and can be attached to the exterior surface of the chamber in the same manner as described above with regard to the at least one sensor. The actuator is paired with the microcontroller and is configured to signal the microcontroller to initiate the use of the spacer and to initiate collection of the measurement of airflow. The actuator can be pressed and held (e.g., for about one second or less) to wake the microcontroller from a sleep mode and triggers the at least one sensor to initiate the collection of airflow data. In some embodiments, the actuator can be pressed and held (e.g., for about three seconds or more) to pair a Bluetooth® connection with the spacer and a computer (e.g., patient's personal computer or practitioner's computer), as described herein.
In some embodiments, instead of an actuator (e.g., a button), the spacer can include a motion sensor such that when the patient gently shakes the spacer, the at least one sensor can be activated.
As described above, the spacer includes a microcontroller that is disposed on the exterior surface of the chamber as part of the actuator and/or as part of the at least one sensor. The microcontroller processes the airflow data from the at least one sensor and applies a series of calculations to the airflow data such that airflow metrics are calculated. The measurement of airflow includes measuring peak expiratory flow, forced expiratory volume, forced vital capacity, or a combination thereof. From the measurement of airflow, airflow metrics calculated include volumetric airflow (mL/s), airflow volume (mL), forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF). These measurements can be transmitted, stored and logged into a database to create historical metrics for the patient over time, as well as repeated doses of medicaments.
The microcontroller is powered by a battery and cycles between an active mode and a sleep mode in order to conserve battery life of the microcontroller.
The spacer includes a radio, such as, for example, a Bluetooth® radio 46 for wireless connection. The Bluetooth® radio is configured to pair with a Bluetooth® radio 48 of a personal computer such as a smartphone 50 or a computer of the patient and/or the practitioner, as described herein. The Bluetooth® radio transmits the airflow data to the smartphone. In some embodiments, the personal computer can be one of a plurality of devices such as, for example, network/stand-alone computers, personal digital assistants (PDAs), WebTV (or other Internet-only) terminals, set-top boxes, cellular/phones, screenphones, pagers, blackberry, smart phones, iPhone, iPad, table, peer/non-peer technologies, kiosks, or other known (wired or wireless) communication devices, etc.
The Bluetooth® radio attempts to establish a wireless connection with the smartphone which serves as the Bluetooth® receiver before streaming the airflow metrics in real time to the smartphone, as shown in
In some embodiments, the microcontroller of the spacer can send the airflow data and/or airflow metrics to a cloud network. The cloud network is a data network environment in which the airflow data and/or airflow metrics from the microcontroller can be stored in a network-attached storage, instead of being solely stored in a local storage.
In some embodiments, the airflow data and/or airflow metrics collected from the spacer (e.g., microcontroller) can be transmitted to a computer, smartphone, or other database and associated with stored medical record data for the particular patient including, among other things, the patient's name, date of birth, sex, address, name of the medicament prescribed, strength, number of days for the MDI or SMI to be used, quantity dispensed, prescriber name, prescription number, pharmacy where filled, number of refills and/or other information.
The spacer includes indicia, such as LEDs, as disclosed above, located on the exterior surface of the chamber. The LEDs indicate when the spacer is awake, when the spacer is connected to a paired smartphone and when pairing between the spacer and the smartphone is occurring. In some embodiments, the indicia can be one or more LED lights used as visual indicators. In some embodiments, the LEDs can be paired with an audio signature such as a buzzer or tune. The indicia may also include unique indicia comprising at least one color, letter, sound, light, and/or video. In some embodiments, the LEDs can be various colors, such as, for example, blue, red, yellow, white, green, purple, pink and/or orange.
In some embodiments, the spacer comprises a display 53, as shown in
The smartphone is loaded with a software program (e.g., smartphone application) that stores the airflow data/metrics and interfaces with the patient such that the airflow data/metrics can be searched, retrieved and displayed by the patient and/or the practitioner. The software program can also be associated with a message digest with a date and time stamp of medicament use that can be a part of a history log of metrics for that patient. The date and time of medicament use is confirmed when the actuator is pressed and when the at least one sensor indicates airflow via patient inhalation. In some embodiments, the airflow data can also be transmitted via Wi-Fi to a web dashboard on a computer 54. The web dashboard generates a report for the medical practitioner.
In some embodiments, the airflow data may be downloaded in one or more textual/graphical formats (e.g., RTF, PDF, TIFF, JPEG, STL, XML, XDFL, TXT etc.), or set for alternative delivery to the smartphone and/or the web dashboard of the computer. The patient may view the airflow data results at a user interface, which allows viewing on the same display, such as the screen 56 or monitor 58 of the smartphone and/or the computer.
In some embodiments, the patient and/or the practitioner can interface with the computer (e.g., smartphone, a computer of the practitioner etc.) via a user interface that may include one or more display devices (e.g., CRT, LCD, or other known displays) or other output devices (e.g., printer, etc.), and one or more input devices (e.g., keyboard, mouse, stylus, touch screen interface, or other known input mechanisms) for facilitating interaction of the patient and/or the practitioner with the airflow data from the smart spacer via the user interface. The user interface may be directly coupled to an airflow database or directly coupled to a network server system via the Internet or cloud computing.
In some embodiments, the user interface device may be implemented as a graphical user interface (GUI) containing a display or the like, or may be a link to other user input/output devices known in the art. Individual or of a plurality of devices (e.g., network/stand-alone computers, personal digital assistants (PDAs), WebTV (or other Internet-only) terminals, set-top boxes, cellular/phones, screenphones, pagers, blackberry, smart phones, iPhone, iPad, table, peer/non-peer technologies, kiosks, or other known (wired or wireless) communication devices, etc.) may similarly be used to execute one or more computer programs (e.g., universal Internet browser programs, dedicated interface programs, etc.) to allow patients to interface with the airflow data in the manner described. Database hardware and software can be developed for access by patients and/or practitioners through personal computers, mainframes, and other processor-based devices. Patients and/or practitioners may access the data stored locally on hard drives, CD-ROMs, stored on network storage devices through a local area network, or stored on remote database systems through one or more disparate network paths (e.g., the Internet).
In some embodiments, the electronic circuitry in the spacer, may include some or all of the capabilities of a computer (e.g., the microcontroller) in communication with a network and/or directly with other computers. The computer may include a processor, a storage device, a display or other output device, an input device, and a network interface device, all connected via a bus. A battery can be provided to couple and power the computer. The computer may communicate with a network. The processor represents a central processing unit of any type of architecture, such as a CISC (Complex Instruction Set Computing), RISC (Reduced Instruction Set Computing), VLIW (Very Long Instruction Word), or a hybrid architecture, although any appropriate processor may be used. The processor executes instructions and includes that portion of the computer that controls the operation of the entire computer. The processor typically includes a control unit that organizes data and program storage in memory and transfers data and other information between the various parts of the computer. The processor receives input data from the input device (e.g., the at least one sensor) and the network reads and stores instructions (for example processor executable code) and data in a main memory, such as random access memory (RAM), static memory, such as read only memory (ROM), and a storage device. The processor may present data to a user via an output device or user interface, as described above, such as the screen of the smartphone or the monitor of the web dashboard of the practitioner's computer or on the display that is located on the spacer.
In some embodiments, the spacer is reusable and washable. The spacer and its components can be made from various materials, such as, for example, plastic, such as a thermoplastic material. In some embodiments, materials include, but are not limited to thermoplastics such as polyaryletherketone (PAEK) including polyetheretherketone (PEEK), polyetherketoneketone (PEKK) and polyetherketone (PEK), carbon-PEEK composites, PEEK-BaSO4 polymeric rubbers, polyethylene terephthalate (PET), polyurethane, silicone-polyurethane copolymers, polymeric rubbers, polyolefin rubbers, semi-rigid and rigid materials, elastomers, rubbers, thermoplastic elastomers, thermoset elastomers, elastomeric composites, rigid polymers including polyphenylene, polyamide, polyimide, polyetherimide, polyethylene, epoxy and their combinations.
In some embodiments, the spacer and its components can be sterilized by radiation via terminal sterilization. Terminal sterilization of a product provides greater assurance of sterility than from processes such as an aseptic process, which requires individual product components to be sterilized separately and the final package assembled in a sterile environment.
In various embodiments, gamma radiation is used in the terminal sterilization step, which involves utilizing ionizing energy. Gamma rays are highly effective in killing microorganisms, they leave no residues, nor do they have sufficient energy to impart radioactivity to the spacer. Gamma rays can be employed when the spacer is in a package and gamma sterilization does not require high pressures or vacuum conditions, thus, package seals and other components are not stressed. In addition, gamma radiation eliminates the need for permeable packaging materials.
In various embodiments, electron beam (e-beam) radiation may be used to sterilize one or more components of the spacer. E-beam radiation comprises a form of ionizing energy, which is generally characterized by low penetration and high-dose rates. E-beam irradiation is similar to gamma processing in that it alters various chemical and molecular bonds on contact, including the reproductive cells of microorganisms. Beams produced for e-beam sterilization are concentrated, highly-charged streams of electrons generated by the acceleration and conversion of electricity.
The smart spacer of the current application can provide at least three functions into a single device. These functions include, medicament utilization tracking, inhalation technique coaching and lung health tracking, as described below. The spacer includes an inhalation mode and an exhalation mode to perform these functions. The inhalation mode is associated with utilization tracking and inhalation technique coaching and the exhalation mode functions as a spirometer, as described below which is associated with the function of lung health tracking.
Inhalation Mode: Medicament Utilization Tracking
In the inhalation mode for medicament utilization tracking, as shown in
Inhalation Mode: Inhalation Technique Coaching
The inhalation technique coaching function indicates whether a patient is breathing too shallow and can assist the patient in learning how to breathe deeply and slowly. In operation, as shown by the flowchart of
The spacer is used to track the inhalation technique of the patient such that when the at least one sensor detects the direction of airflow, volumetric flow rate is measured throughout the duration of inhalation. From airflow data compiled, the microcontroller calculates the total inhaled volume and duration which is then used guide the patient on inhalation technique through an application of a personal computer, such as a smartphone. The practitioner can also view these results via a web dashboard, as described above.
In some embodiments, the application on the personal computer or the display on the spacer can also display phrases that show patient progress or regression. For example, the phrases can include, but are not limited to “good job,” “please inhale deeper,” “please slow down,” and/or “please stop.” Longitudinal graphs on patient progress can also be displayed.
In addition to the airflow data, inhalation technique coaching also factors in the body weight and height of the patient, title volume (TV), and inhalation time.
The at least one sensor detects airflow via its direction, and volumetric flow rate is measured throughout the duration of the inhalation. In some embodiments, airflow data measured by the at least one sensor is sent to the microcontroller such that the microcontroller can store data and can implement calculations for determining airflow metrics. The data is then transmitted and received 510. The data is saved in internal memory of the microcontroller with a date and time stamp. The data is then sent to the patient's smartphone and/or the web dashboard of the practitioner's computer. The data is used to guide the patient on their inhaler technique via the patient's smartphone loaded with an application (e.g., did the patient breathe slow enough and did they breathe deep enough). The MDI can be actuated again 504, and the steps repeated. Further, after the data is transmitted and received, the patient can repeat these steps and go back to inserting a different inhaler (MDI) 500. If no other input occurs, then the spacer will go into a sleep mode 512.
Exhalation Mode: Lung Health Tracking
The spacer can be used in the exhalation mode as a spirometer. This will be where the inhaler has been removed from the spacer and, in some embodiments, the distal end opening remains open and is unobstructed by the inhaler. In some embodiments, the spacer as a spirometer can perform a pulmonary function test (PFT) which measures lung capacities of patients. A spirometer measures values of forced vital capacity (FVC), FEV1, PEF, flow volume ring, maximum voluntary ventilation (MVV), maximal inspiratory/expiratory pressures (MIP/MEP), airway resistance (Raw) and compliance (C), functional residual capacity (FRC), total lung capacity (TLC), residual volume (RV) FRC/TLC ratio, minute ventilation, alveolar ventilation and dead space, ventilation distribution, and diffusion capacity upon the patient performing different breathing maneuvers.
In PFT, as the patient exhales air into the spacer acting as a spirometer, the volume, intensity, and flow of air at different times will be measured by the at least one sensor. Parameters of FVC and forced expiratory volume in one second are mostly used in dynamic ventilation tests and can be performed by using the spacer in the spirometry mode. In the mentioned tests, the volume of air exhaled from the lungs by breathing out enforcedly, quickly and deeply is measured. The volume of air expired by the patient in the first second is measured by FEV1 value. The FEV value can be used in volume-time graphs. The patient's volume of expiration by time can be visualized by means of the volume-time graphs and it is examined by making comparison where it is located in the required curve. Also, a flow-time curve is examined in PFT. A volume-time curve is created by measuring the expiration of the patient and the flow generated within the spacer. The flow-volume curve is used for an interpretation of the factors affecting the flow occurring in airways. The top of the flow-volume curve indicates the maximum expiratory flow rate (peak expiratory flow (PEF). PEF value indicates diameter of large airways and activity of respiratory muscles. Evaluation and interpretation of PFT result are performed through the comparison of the measured values to the expected values. The expected values used in test evaluation are obtained as a result of studies carried out with healthy persons of different age, gender, height, weight, and race groups.
If the at least one sensor detects via the direction of airflow that the patient has begun exhaling, then the volumetric airflow rate is measured throughout the duration of the exhalation 304. From data compiled, the microcontroller of the spacer calculates airflow metrics or lung health metrics 306 such as forced expiratory volume within the first second of exhalation (FEV1) and peak expiratory flow (PEF). The results are then displayed on a longitudinal graph with interpreted metrics through an application of a personal computer, such as a smartphone and/or the practitioner can view the results via a web dashboard 308.
In some embodiments, the medicament (API) can be dispensed from an inhaler such as a metered-dose inhaler (MDI) or a soft mist inhaler (SMI). The medicament (API) can be any medicament suitable for inhalation including an anticholinergic agent, a bronchodilator, and/or a corticosteroids.
The anticholinergic agents include, but are not limited to trihexyphenidyl, benztropine mesylate, ipratropium, tiotropium, orphenadrine, atropine, flavoxate, oxybutynin, scopolamine, hyoscyamine, tolterodine, belladonna alkaloids, fesoterodine, solifenacin, darifenacin, propantheline, 5-[3-(3-Hydroxyphenoxy)azetidin-1-yl]-5-methyl-2,2-diphenylhexanamide or a combination thereof. The bronchodilators include, but are not limited to adrenergic bronchodilators including, but not limited to, levalbuterol, metaproterenol, pirbuterol, formoterol, terbutaline, or albuterol; anticholinergic bronchodilators including, but not limited to, aclidinium systemic, ipratropium systemic, tiotropium systemic, orumeclidinium systemic; bronchodilator combinations including, but not limited to, umeclidinium/vilanterol systemic, budesonide/formoterol systemic, fluticasone/salmeterol systemic, albuterol/ipratropium systemic, fluticasone/vilanterol systemic, olodaterol/tiotropium systemic, formoterol/mometasone systemic, formoterol/glycopyrrolate systemic, orglycopyrrolate/indacaterol systemic; and methylxanthines including, but not limited to, theophylline systemic, aminophylline systemic, or dyphylline systemic. The corticosteroids include, but are not limited to, beclomethasone, budesonide, flunisolide, fluticasone, mometasone, ciclesonide or tiotropium.
The medicament (API) may include the medicaments (APIs) described above, and may also include substances traditionally regarded as actives, drugs and bioactive agents, as well as biopharmaceuticals typically employed to treat a number of conditions which is defined broadly to encompass diseases, disorders, infections, and the like. Exemplary medicaments (APIs), without limitation, antibiotics, antivirals, H2-receptor antagonists, 5HT1 agonists, 5HT3 antagonists, and COX2-inhibitors.
In some embodiments, the medicaments (APIs) may also be selected from, analgesics, e.g., codeine, dihydromorphine, ergotamine, fentanyl or morphine; anginal preparations, e.g., diltiazem; antiallergics, e.g., cromoglycate (e.g. as the sodium salt), ketoprofen or nedocromil (e.g. as the sodium salt); antiinfectives e.g., cephalosporins, penicillins, streptomycin, sulphonamides, tetracyclines and pentamidine; antihistamines, e.g., methapyrilene; anti-inflammatories, e.g., beclomethasone (e.g. as the dipropionate ester), fluticasone (e.g. as the propionate ester), flunisolide, prednisone, prednisolone, budesonide, rofleponide, mometasone e.g. as the furoate ester), ciclesonide, triamcinolone (e.g. as the 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 free base or 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; 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. It will be clear to a person skilled in the art that, where appropriate, the medicaments (APIs) 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 optimize the activity and/or stability of the medicament.
Additionally, the medicaments (APIs) may be selected from, for example, antibiotics. Such antibiotics include, for example, nitroimidazole antibiotics, tetracyclines, penicillins, cephalosporins, carbopenems, aminoglycosides, macrolide antibiotics, lincosamide antibiotics, 4-quinolones, rifamycins and nitrofurantoin. In the following examples of such antibiotics are listed: ampicillin, amoxicillin, benzylpenicillin, phenoxymethylpenicillin, bacampicillin, pivampicillin, carbenicillin, cloxacillin, cyclacillin, dicloxacillin, methicillin, oxacillin, piperacillin, ticarcillin, flucloxacillin, cefuroxime, cefetamet, cefetrame, cefixine, cefoxitin, ceftazidime, ceftizoxime, latamoxef, cefoperazone, ceftriaxone, cefsulodin, cefotaxime, cephalexin, cefaclor, cefadroxil, cefalothin, cefazolin, cefpodoxime, ceftibuten, aztreonam, tigemonam, erythromycin, dirithromycin, roxithromycin, azithromycin, clarithromycin, clindamycin, paldimycin, lincomycirl, vancomycin, spectinomycin, tobramycin, paromomycin, metronidazole, tinidazole, ornidazole, amifloxacin, cinoxacin, ciprofloxacin, difloxacin, enoxacin, fleroxacin, norfloxacin, ofloxacin, temafloxacin, doxycycline, minocycline, tetracycline, chlortetracycline, oxytetracycline, methacycline, rolitetracyclin, nitrofurantoin, nalidixic acid, gentamicin, rifampicin, amikacin, netilmicin, imipenem, cilastatin, chloramphenicol, furazolidone, nifuroxazide, sulfadiazin, sulfametoxazol, bismuth sub salicylate, colloidal bismuth subcitrate, gramicidin, mecillinam, cloxiquine, chlorhexidine, dichlorobenzylalcohol, methyl-2-pentylphenol. The active antibiotics could be in standard forms or used as salts, hydrates, esters etc. A combination of two or more of the above listed drugs may be used. The antibiotics can be clarithromycin, erythromycin, roxithromycin, azithromycin, amoxicillin, metronidazole, tinidazole and tetracycline. Clarithromycin and metronidazole alone or in combination are especially suitable.
Moreover, medicaments (APIs) may also be selected from, for example, antivirals. Examples of APIs that are effective for the treatment of viral and viral associated conditions are (1-alpha, 2-beta, 3-alpha)-9-[2,3-bis(hydroxymethyl)cyclobutyl]guanine [(−)BHCG, SQ-34514, lobucavir], 9-[(2R,3R,4S)-3,4-bis(hydroxymethyl)-2-oxetanosyl]adenine(oxetanocin-G), acyclic nucleosides, for example acyclovir, valaciclovir, famciclovir, ganciclovir, and penciclovir, acyclic nucleoside phosphonates, for example (S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl)cytosine (HPMPC), [[[2-(6-amino-9H-purin-9-yl)ethoxy]methyl]phosphinylidene]bis(oxymethylene)-2,2-dimethylpropanoic acid (bis-POM PMEA, adefovir dipivoxil), [[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl]phosphonic acid(tenofovir), and (R)-[[2-(6-Amino-9H-purin-9-yl)-1-methylethoxy]methyl]phosphonic acid bis-(isopropoxy carbonyloxymethyl)ester (bis-POC-PMPA), ribonucleotide reductase inhibitors, for example 2-acetylpyridine 5-[(2-chloroanilino)thiocarbonyl)thiocarbonohydrazone and hydroxyurea, nucleoside reverse transcriptase inhibitors, for example 3′-azido-3′-deoxythymidine (AZT, zidovudine), 2′,3′-dideoxycytidine (ddC, zalcitabine), 2′,3′-dideoxyadenosine, 2′,3′-dideoxyinosine (ddI, didanosine), 2′,3′-didehydrothymidine (d4T, stavudine), (−)-beta-D-2,6-diaminopurinedioxolane (DAPD), 3′-azido-2′,3′-dideoxythymidine-5′-H-phosphophonate (phosphonovir), 2′-deoxy-5-iodo-uridine(idoxuridine), (−)-cis-1-(2-hydroxymethyl)-1,3-oxathiolane 5-yl)-cytosine(lamivudine), cis-1-(2-(hydroxymethyl)-1,3-oxathiolan-5-yl)-5-fluorocytosine(FTC), 3′-deoxy-3′-fluorothymidine, 5-chloro-2′,3′-dideoxy-3′-fluorouridine, (−)-cis-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol(abacavir), 9-[4-hydroxy-2-(hydroxymethyl)but-1-yl]guanine(H2G), ABT-606 (2HM-H2G) and ribavirin, protease inhibitors, for example indinavir, ritonavir, nelfinavir, amprenavir, saquinavir, (R)—N-tert-butyl-3-[(2S,3S)-2-hydroxy-3-N—[(R)-2-N-(isoquinolin-5-yloxyacetyl)amino-3-methylthio-propanoyl]amino-4-phenylbutanoyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxamide (KNI-272), 4R-(4alpha, 5 alpha,6beta)]-1,3-bis[(3-aminophenyl)methyl]hexahydro-5,6-dihydroxy-4,7-bis(phenylmethyl)-2H-1,3-diazepin-2-one dimethanesulfonate(mozenavir), 3-[1-[3-[2-(5-trifluoromethylpyridinyl)-sulfonylamino]phenyl]propyl]-4-hydroxy-6alpha-phenethyl-6beta-propyl-5,6-dihydro-2-pyranone(tipranavir), N′-[2(S)-Hydroxy-3 (S)—[N-(methoxycarbonyl)-1-tert-leucylamino]-4-phenylbutyl-Nalpha-(methoxycarbonyl)-N′-[4-(2-pyridyl)benzyl]-L-tert-leucylhydrazide(BMS-232632), 3-(2(S)-Hydroxy-3 (S)-(3-hydroxy-2-methylbenzamido)-4-phenylbutanoyl)-5,5-dimethyl-N-(2-methylbenzyl)thiazolidine-4(R)-carboxamide(AG-1776), N-(2(R)-hydroxy-1(S)-indanyl)-2(R)-phenyl-methyl-4(S)-hydroxy-5-(1-(1-(4-benzo[b]furanylmethyl)-2(S)—N′-(tert-butylcarboxamido)piperazinyl)pentanamide (MK-944A), and (3S)-tetrahydrofuran-3-yl (1S,2R)-[[(4-aminophenyl)sulphonyl)](isobutyl)amino]-1-benzyl-2-(phosphonooxy)propylcarbamate monocalcium salt(fosamprenavir), interferons such as α-interferon or a combination thereof.
The medicament may also include pharmaceutically acceptable salts, esters, solvates, and/or hydrates of the pharmaceutically active substances referred to hereinabove. Various combinations of any of the above medicaments may also be employed.
The medicament further comprises an excipient and can comprise glucose, arabinose, lactose, sucrose, maltose, mannitol, dextrans, magnesium stearate, leucine, isoleucine, lysine, valine, methionine, phenylalanine, or a combination thereof. In some embodiments, the lactose is lactose monohydrate. In some embodiments, the excipient can include, but is not limited to, monosaccharides such as galactose, mannose, sorbose; disaccharides such as lactose, sucrose and trehalose and the like; polysaccharides such as starch, raffinose, dextran and the like; and mixtures thereof. In some embodiments, the at least first layer and/or the at least second layer can comprise more than one excipient.
In some embodiments, the inhaler does not require a propellant. However, in some embodiments, the inhaler can contain propellants, including, but not limited to hydrofluoroalkane (HFA), such as chlorodifluoromethan, trifluoromonofluoroethane, chlorodifluoroethane, difluoroethane, heptafluoropropane or a combination thereof.
The present disclosure also provides methods of making a spacer, the method comprising providing a spacer comprising a chamber having an interior surface, an exterior surface, and a proximal opening and a distal opening opposite the proximal opening, the interior surface of the chamber configured to receive inhalation air and exhalation air from a patient, attaching to the interior surface of the chamber at least one sensor for measuring airflow in the chamber; and attaching an actuator on the exterior surface of the chamber, the actuator configured to initiate measurement of airflow in the chamber. It is to be understood that the spacer described is the spacer of
In some embodiments, a method of using a spacer is provided. The method comprises attaching an inhaler to a distal end opening of the spacer, the spacer comprising a chamber having an interior surface and an exterior surface, the interior surface of the chamber configured to receive aerosolized medicament from an inhaler and having at least one sensor for measuring airflow in the chamber; and an actuator disposed on the exterior surface of the chamber configured to initiate measurement of airflow in the chamber. It is to be understood that the spacer described is the spacer of
In some embodiments, the spacer comprises a display on the exterior surface that displays indicia to instruct a patient to inhale, exhale, or aerosolize the medicament. In some embodiments, the method further comprises contacting the actuator to initiate the at least one sensor to collect airflow data and contacting the inhaler to aerosolize the medicament in the chamber.
In some embodiments, a method of using a spacer is provided. The method comprises removing an inhaler from a distal end opening of the spacer, the spacer having a chamber having an interior surface and an exterior surface, the interior surface of the chamber configured to receive inhalation air and exhalation air from a patient, the interior surface having at least one sensor for measuring airflow in the chamber; and an actuator disposed on the exterior surface of the chamber configured to initiate measurement of airflow in the chamber. It is to be understood that the spacer described is the spacer of
In some embodiments, the spacer comprises a display on the exterior surface that displays indicia to instruct a patient to inhale, exhale, or show measurement of airflow in the chamber from the at least one sensor. In some embodiments, the method further comprises contacting the actuator to initiate the at least one sensor to collect airflow data and causing the display to display indicia to instruct the patient to inhale or exhale.
In some embodiments, the smart spacer can be used in a method of treating, diagnosing or prognosing the following diseases, asthma, bronchitis, emphysema and/or COPD.
It will be apparent to those skilled in the art that various modifications and variations can be made to various embodiments described herein without departing from the spirit or scope of the teachings herein. Thus, it is intended that various embodiments cover other modifications and variations of various embodiments within the scope of the present teachings.
This application claims priority to U.S. Provisional Application Ser. No. 62/526,555 filed on Jun. 29, 2017, the entire contents of which is incorporated herein by reference in its entirety.
