CA2829043C - Medicant delivery system - Google Patents
Medicant delivery system Download PDFInfo
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- CA2829043C CA2829043C CA2829043A CA2829043A CA2829043C CA 2829043 C CA2829043 C CA 2829043C CA 2829043 A CA2829043 A CA 2829043A CA 2829043 A CA2829043 A CA 2829043A CA 2829043 C CA2829043 C CA 2829043C
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- precise
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- liquid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
- A61M11/04—Sprayers or atomisers specially adapted for therapeutic purposes operated by the vapour pressure of the liquid to be sprayed or atomised
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/06—Inhaling appliances shaped like cigars, cigarettes or pipes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. ventilators; Tracheal tubes
- A61M16/10—Preparation of respiratory gases or vapours
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pulmonology (AREA)
- Emergency Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Infusion, Injection, And Reservoir Apparatuses (AREA)
- Catching Or Destruction (AREA)
Abstract
Description
TECHNICAL FIELD
[0001] This invention relates to devices and methods for vaporizing a liquid for inhalation. More specifically, the invention relates to providing a device and method for controlling, metering and measuring precise volumes of fluid vaporized and the vapor produced by a hand-held vaporizing device each time the device is engaged by its user that is reliable and safer to use than current devices relying on lithium ion chemistry.
BACKGROUND
Similarly, a precise measured "dose" may be desired, or even required for these substances.
Lithium chemistry batteries, however, are volatile, hazardous (both in that they can release noxious vapors as well as potential for explosion under certain conditions) and environmentally challenging with respect to storage, reliability, and disposability.
SUMMARY
BRIEF DESCRIPTION OF DRAWINGS
DETAILED DESCRIPTION OF THE INVENTION
It is to be understood, however, that the same or equivalent functions and sequences may be accomplished by different embodiments that are also intended to be encompassed within the spirit and scope of the invention.
provided by the vaporizer. As used in the claims, the term "medicant" means a medicament, medication, medicine, pharmaceutical, drug, and the like used for healing, treating, altering, improving, restoring, relieving, and/or curing a particular condition, disease, or mental or physical state, which includes the active ingredient or combination of active ingredients and inactive ingredients infused into an expedient or dissolved in some other carrier.
Since the amount of power supplied to a heating element 152 correlates with the resistance through the heating element, the processor 500 may be programmed to monitor the resistance of the heating element 152 as a proxy for the amount of power being supplied to the heating element 152. Knowing the resistance, the processor 500 can govern the amount of power to supply to the heating element 152. Measuring the resistance at the heating element has several advantages. First, power may be accurately measured and maintained.
Second, it measures the resultant voltage from the circuit, rather than measuring it from the battery, which conserves battery life. Third, it insures that vaporization remains constant, allowing for measured dosages irrespective of the life cycle of the battery and degradation of the heating element.
and A/D functions may also be used to allow the measurement of either the current flow (direct drive) or voltage in the power storage (supercap). When all conditions are met, the control logic 604 activates the discharge switch 610 to heat the vaporization element 612.
the processor 604 from an ultra-low power sleep mode. The fluid discharge actuator 616 may be a mechanical device to activate the system, such as a turn switch, a button, knob, lever, and the like.
Therefore, using the lower current draw from the batteries and the power storage stage 608 allows for a high current event without unduly draining the batteries.
This power saving feature with the power state can be accomplished via either an ultra-low power mode of the conversion/cpu or a power disconnect/latch function. This is used to extend the operation life of the device after the first use.
Therefore, the power control system 306 may also comprise a means for controlling a precise duration of time to supply the precise amount of power to completely vaporize the predetermined volume of liquid at the required temperature. The means for controlling a precise duration of time to supply the power may comprise a "one-shot" control circuitry 170, 172, or 174 that can be integrated with the circuit for controlling the amount of power described above. Examples of "one-shot" circuits 170, 172, or 174 are shown in Figures 15-17 and described below in more detail. A "one-shot" circuit may be used to limit the electric current delivery time interval regardless of how long the user holds the lever down.
The power control system 306 is completely "off" in between uses; therefore, there is no drain on the battery during idle time. As a result, battery life is prolonged.
Therefore, an efficient medicant delivery device may comprise a power control system 34 utilizing various embodiments of the circuitry described above to control the efficient and effective use of power, and/or a fluid delivery system 30, 302, or 402 as a means for consistently metering a precise volume of a liquid from the fluid reservoir to precisely control the volume of the liquid discharged for vaporization. Various combinations of these systems may be used to achieve the desired level of accuracy. An atomization or vaporization system 32 may also be required to vaporize the medicant. In this application, atomization and vaporization are referred to interchangeably to indicate that the state of the medicant is a form that can be inhaled and absorbed by the lungs.
Alternatively, in some embodiments, the precise volume may vary depending on the temperature of the wire and how long the wire remains energized at that temperature.
Controlling the volume of the medicant discharged also improves the metering accuracy.
Examples of devices for controlling the volume of medicants to a heating element for vaporization are described below. These devices can be used alone or in combination with the power control system to further improve the accuracy of metered doses of medicants.
Referring further to Figures 3-5, an embodiment of the device 20 includes a fluid or liquid delivery system 30 as the means for consistently metering a precise volume of a liquid to precisely control the volume of the liquid discharged for vaporization, and a vaporizing system 32, as well as an electrical power control system 34. The electrical power control system 34 may include batteries 44 within a battery compartment 42 of the housing 22, and with the batteries electrically connected to a flexible circuit board 82 via a spring 46 and contacts 48. As shown in Figure 5, the housing may be provided with left and right sides, in a clamshell design. The lever 28 may be attached to the housing 22 at a pivot 58.
lever segment 67 of the tube 66 is positioned beneath the lever 28 and a fixed rigid surface inside of the housing, which optionally may be part of the circuit board 82 on which power management circuitry is located. Locating features 112 may be provided in, on, or through the circuit board 82 to ensure desired positioning is maintained. The lever 28 is retained by lever pivot 116 and can pivot through a controlled range of motion.
Referring to Figure 4, as the lever 28 pivots down about the pivot 58, a pincher 86 located on a first section 90 pivotally attached to the housing pinches the pump segment 67 of the tube 66 against an inside surface of the housing 22, adjacent to the pivot 58 and the reservoir 64. This temporarily closes off the tube 66 at the pincher 86. As the lever 28 continues to pivot down (or inward towards the centerline of the device) a ramp surface 88 on a second section 92 of the lever 28, flexibly attached to the first section, progressively squeezes the pump segment 67 of the tube 66 between the pincher 86 and the lever valve 70. This creates a squeegee type of movement which pumps liquid towards the lever valve 70 using a peristaltic action. As the lever 28 continues to pivot inwardly, posts on the lever press the valve washer 76 down against the force of the valve spring 72. This temporarily opens the lever valve 70 by allowing the valve section 80 of the tube 66 to open. With the valve section 80 of the tube open, and with liquid in the tube being pumped via the ramp surface 88, a bolus of liquid flows through the valve section 80 and the outlet segment 154 and into the wire coil 152.
The current supplied to the wire coil, and the temperature of the wire coil when operating, may be regulated by the circuit board, depending on the liquid used, the desired dose, and other factors. The switch 158 may be positioned to close only when the lever 28 is fully depressed. This avoids inadvertently heating the wire coil. It also delays heating the wire coil until the bolus of liquid is moved into the wire coil via the pivoting movement of the lever, to help prolong battery life. A "one-shot" control circuit 170, for example, as shown in Figure 15 described below, may be used to limit the electric current delivery time interval regardless of how long the user holds the lever down. The power is completely "off" in between uses. There is no drain on the battery during idle time. As a result, battery life is prolonged.
This allows the device 20 to be used in any orientation, since gravity is not needed to keep the released dose of liquid in place.
Force exerted on the reservoir 64 by the foam trying to recover to its relaxed state exerts compressive force on the reservoir which maintains the liquid in the reservoir under pressure. The foam pad 106 may be used in place of the springs 60 shown in Figure 4.
The reservoir may alternatively be pressurized using a syringe with a spring-biased plunger. With any of these designs, the reservoir may optionally be provided as a replaceable cartridge.
Furthermore, sealing of the vaporizer system with a valve such as the valve 70 or 118 that is only actuated at the time of delivery, and positive pressure dispensing prevents inadvertent leakage of liquid irrespective of orientation of the device during storage or use, thereby providing a means for consistently metering a precise volume of a liquid from the fluid reservoir to precisely control the volume of the liquid discharged for vaporization.
(pin 10) goes high and Cl is rapidly charged to near the supply voltage through a FET
within Ul. At the same time, resistor R1 is switched to a logical "0" state and immediately begins discharging capacitor Cl with the time constant of 1/RC.
However, more precise metering of the medicant may be accomplished by increasing the current pulse duration as the current decreases over the discharge life of the battery. In the circuit 172 shown in Figure 16, an additional OP amp IC serves as a voltage controlled current source for the power control system. The input voltage is sampled from Pin 10 of U1. A constant current is generated in Q3 and used to discharge the timing capacitor, Cl, at a constant rate. Once the voltage across Cl reaches the logic threshold, CD
4047 trips and the output pulse width is complete. As the battery voltage decreases the constant current generated in Q3 decreases, causing the time to discharge Cl to increase. This lengthens the output pulse to maintain a relatively constant heater power per inhalation cycle as the battery voltage declines over the lifetime of the device. The various current setting and sense resistor values may be adjusted to provide optimal performance. Other circuits may be employed to provide the same function such as voltage to frequency converters.
This keeps the filament voltage constant throughout the battery life. The regulated voltage may be chosen to optimize the heater operation near end of life. A low dropout regulator is desired to maximize the lifespan before regulation is no longer maintained.
A simple linear regulator is shown, but a high efficiency, switching regulator may also be employed to improve efficiency. The pulse duration is maintained as described above or an equivalent "one shot" circuit and the heater current is kept constant by the voltage regulator.
heating element such as ni-chrome wire can be coiled around the tube, coiled into the tube or inserted into a tube in a V-shape so as to heat the entire volume of liquid at the same time.
As a result, the device cannot be inadvertently turned on during shipping and storage.
Battery life is therefore better preserved. Before operating the vaporizing device 200 for the first time, the user pulls the tab out of the slot 210. As shown in Figures 19 and 20, the mouthpiece is round. The dimension LL in Figure 20 between the coil 222 and the mouthpiece tip may be minimized to 15, 10 or 5 mm. The liquid reservoir may have a volume exceeding 0.8 or 1.0 ml to allow foam compression to pressurize the pump. In the device 200, the liquid supplied from the reservoir via the tube 236 is not delivered into the coil 222. Rather the liquid is delivered onto the wick 220. The heating coil 222 abuts the wick 220 and heats the wick, which then vaporizes substantially all of the liquid on or in the wick.
By regulating the size of the vapor molecule produced, the vaporizing devices can be used with more precision and with fluids and medicants that require carefully controlled dosages particle sizes. In some cases, smaller molecules may be advantageous as they can be inhaled more deeply into the lungs, providing better a more effective delivery mechanism.
The fabric can be manufactured with a desired mesh opening size, to regulate the size of the vapor particles and/or molecules delivered by the vaporizer. By controlling the amount of electrical power and the duration of power to the heater, the heater continues to vaporize the fluid delivered to the heater until the vapor particles are small enough to pass through the mesh of the fabric. Containing the fluid inside the fabric with the heater until the particles are sufficiently small enough to pass through the fabric can help to effectively atomize and deliver all the fluid delivered to the heater, with little or no waste, in turn controlling the dose.
The proximal end 316 is configured to accept the piston 312 which forms a hydraulic seal against the walls of the reservoir 310, such that the medicant cannot leak past the piston 312. The piston 312 may have a hollow core 313. A plunger 320 is provided to couple with the piston 312 to drive the piston 312 forward in a controlled and step-like manner.
The plunger 320 comprises a shaft 322 having a head 324 at one end. In a preferred embodiment, the head 324 is flanged. The head 324 is configured to engage with mating geometry on the inside of the piston 312, securing the piston 312 to the plunger 320. The shaft 322 of the plunger is configured with a male screw thread 326, preferably, for its entire length.
Various features of the housing 308 and reservoir 310 constrain the position of the drive nut 328 such that it is free to move rotationally concurrent to the axis A of the plunger 320, but prevent translation in any other direction. The drive nut 328 has a mating female screw thread 330 to the plunger 320 and is threaded onto the plunger 320. The drive nut 328 is further configured with ratchet teeth 332, which interact with a pawl 334 on a button 314 described later such that during operation, the drive nut 328 will rotate in a single direction.
Preferably, the cap 336 is made of silicone. The outlet 338 is responsive to pressure from the medicant within the reservoir 310 such that when the medicant is at a higher pressure than the ambient pressure outside of the reservoir 310, the outlet 338 will open 338A, allowing medicant to escape the reservoir 310. Once enough medicant has escaped the reservoir 310 to equilibrate with ambient pressure, the outlet 338 will automatically collapse, sealing the remaining contents of the reservoir 310 from ambient, thereby, preventing loss of medicant to evaporation. So, the measured dose is determined by proper calibration of the pressure needed to properly form and maintain a droplet of the medicant at the outlet 338 until vaporization is initiated. The nature of seal is such that pressure changes external to the device will not cause the reservoir to come "unsealed"
the external pressure changes would not be focused enough nor forceful enough to "unseal."
And, the natural elasticity of the reservoir would cause the seal to "re-seal"
irrespective of external pressure changes.
The button 314 is constrained such that it can translate in a direction normal to the control surface 340 when it is pressed. The button 314 is configured with two spring elements 341a, 341b which bias the button back to its neutral position in the absence of pressure on the control surface 340. The spring elements 341a, 341b are designed to deform under pressure on the load surface and return to their original shape upon release of that pressure. The range of button travel motion is limited by a stop 342 having an upper surface 343a and a lower surface 343b. The stop surfaces 343a, 343b engage opposing surfaces on lower and upper housings at limits of button travel, creating a fixed range of displacement for the button 314 when it is pressed/released. The button 314 is further configured with a pawl 334 to engage ratchet teeth 332 on the drive nut 328. When the button 314 is depressed, the pawl 334 engages ratchet teeth 332, causing the drive nut 328 to rotate. Upon release, a sloped surface 344 of a pawl 334 and an opposing surface 346 of the ratchet 332 oppose one another, deflecting the pawl 334 at a web allowing the pawl 334 to ride over the adjacent ratchet tooth and the button 314 to return to its neutral position. In this manner, the ratchet 332 allows the drive nut 328 to rotate in a single direction.
This closure serves to initiate a power cycle to the vaporization system 32 as described later. In some embodiments, the contacts 350a, 350b may be directly under the spring elements 341a, 341b. The underside of the spring elements 341a, 341b may have independent contact pins 348 to connect with the contacts 350a, 350b to close the circuit.
In some embodiments, a single contact pin 348 and a single contact 350a may be used.
In the preferred embodiment, the circuit board 362 comprises a one-shot circuit (similar to or same as the circuitry described above) that delivers a fixed and precise amount of power to the nichrome heater 152 with each actuation, the amount of power delivered being that necessary to atomize the delivered bolus of medicant.
Without the circuitry to precisely control the power, decreased battery power would lead to a lower temperature wire 152 for a given activation. In such case, if the volume of the medicant remains the same, then there may be incomplete vaporization of the medicant.
The housing 408 has a top end 410 and a bottom and 412 opposite the top end 410. The top end 410 comprises a cover 414.
The user can then begin the process of inhaling through the inhaler, which starts the heating process by activating a flow sensor.
This assembly provides a secure, tamper resistant chamber for retaining the fluid.
The fluid delivery system 402 is then connected to a gear reduction assembly 424 that allows the linear syringe actuator to be advanced through the reservoir 422 in a consistent amount for each rotation of the knob 418.
The heating element allows the medicant to vaporize; however, prior to exiting through the mouthpiece, the vapor product is filtered through the permeable membrane to govern the size of the vapor product delivered to the user. The membrane should be made of a material that is resilient to heat, such as ceramic or Kevlar material.
The device can be used to deliver dietary supplements, sleep aids, weight loss products, pain killers, and many other prescription or over-the-counter pharmaceutical products where precise dosing is required. The present invention can even be implemented in a non-pharmaceutical context, such as for dispensing liquid candies for consumption, breath fresheners, room fresheners, and any other application where vaporization of a liquid in consistent, reliable, and precise doses are needed.
INDUSTRIAL APPLICABILITY
To avoid changes in the current due to power drainage, the control system utilizes supercapacitors connected to the circuitry. The power source and/or the resistance at the heating element can be monitored so that the system knows how much power needs to be supplied to efficiently vaporize the known volume of medicant. The fluid delivery system utilizes a reservoir and dispensing mechanism that dispenses the same volume of medicant with each actuation. The heating system utilizes a nichrome wire.
Claims (33)
a circuit configured to provide a precise amount of power from a power source to heat a heating element to a minimum required temperature to completely vaporize a precise volume of a liquid, and control a precise duration of time to supply the precise amount of power to completely vaporize the predetermined volume of liquid at the required temperature;
monitor a temperature of the heating element while the power is being supplied;
compare the temperature of the heating element to the minimum required temperature; and adjust the precise duration of time or the precise amount of power based on the comparison step to completely vaporize the liquid, wherein if the precise volume of liquid is adjusted, the precise duration of time or the precise amount of power is adjusted to completely vaporize the adjusted precise volume of liquid within a new minimum required temperature for a new minimum required time.
boost converter and a supercapacitor operatively connected to the power source to adjust the amount of power to the level sufficient to heat the heating element to the required temperature.
a. a housing having a first end and a second end;
b. a mouthpiece attached to the first end;
c. a fluid delivery system;
d. a vaporization system, comprising a heating element in between the mouthpiece and the fluid delivery system; and e. a power control system, comprising a circuit configured to provide a precise amount of power from a power source to heat the heating element to a minimum required temperature to completely vaporize a precise volume of a liquid, control a precise duration of time to supply the precise amount of power to completely vaporize the predetermined volume of the liquid at the required temperature, monitor a temperature of the heating element while the power is being supplied, compare the temperature of the heating element to the minimum required temperature, and adjust the precise duration of time or the precise amount of power based on the comparison step to completely vaporize the liquid, wherein if the precise volume of liquid is adjusted, the precise duration of time or the precise amount of power is adjusted to completely vaporize the adjusted precise volume of liquid within a new minimum required temperature for a new minimum required time.
a. a fluid reservoir inside the housing, the fluid reservoir having a first end and a second end; and b. a pressure generator positioned inside the fluid reservoir at the second end and configured to advance towards the first end incrementally at a fixed and discrete distance to consistently meter a precise volume of a liquid from the fluid reservoir.
a. a piston housed inside the fluid reservoir configured to push the liquid out through the cap; and b. a fluid discharge actuator operatively connected to the piston, wherein actuation of the fluid discharge actuator causes the piston to advance the fixed and discrete distance towards the first end.
a. a housing having a first end and a second end;
b. a mouthpiece attached to the first end;
c. a fluid delivery system, comprising:
i. a fluid reservoir inside the housing, the fluid reservoir having a first end and a second end, and a pressure generator positioned inside the fluid reservoir at the second end and configured to advance towards the first end in at a fixed and discrete distance to consistently meter a precise volume of a liquid from the fluid reservoir;
d. a vaporization system , comprising a heating element in between the mouthpiece and the fluid reservoir; and e. a control system to deliver power to the vaporization system, comprising a circuit configured to provide a precise amount of power from a power source to heat the heating element to a minimum required temperature to completely vaporize a precise volume of a liquid, control a precise duration of time to supply the precise amount of power to completely vaporize the predetermined volume of the liquid at the required temperature, monitor a temperature of the heating element while the power is being supplied, compare the temperature of the heating element to the minimum required temperature, and adjust the precise duration of time or the precise amount of power based on the comparison step to completely vaporize the liquid, wherein if the precise volume of liquid is adjusted, the precise duration of time or the precise amount of power is adjusted to completely vaporize the adjusted precise volume of liquid within a new minimum required temperature for a new minimum required time.
a. a piston housed inside the fluid reservoir configured to push the liquid out through the cap; and b. a fluid discharge actuator operatively connected to the piston, wherein actuation of the fluid discharge actuator causes the piston to advance the fixed and discrete distance towards the first end.
a. determining a precise amount of power required to vaporize the precise volume of liquid with a heating element in a precise duration of time;
b. metering the precise volume of the liquid to the heating element;
c. supplying the precise amount of power from a power supply to heat the heating element for the precise duration of time such that the combination of the precise amount of power and the precise duration of time heats the heating element to a minimum required temperature for a minimum required time to completely vaporize the precise volume of the liquid;
d. monitoring a temperature of the heating element while the power is being supplied;
e. comparing the temperature of the heating element to the minimum required temperature; and f. adjusting the precise duration of time or the precise amount of power based on the comparison step to completely vaporize the liquid, wherein if the precise volume of liquid is adjusted, the precise duration of time or the precise amount of power is adjusted to completely vaporize the adjusted precise volume of liquid within a new minimum required temperature for a new minimum required time.
a. storing the liquid in a fluid reservoir; and b. applying a precise amount of positive pressure inside the fluid reservoir to discharge the precise volume of fluid from the fluid reservoir.
a. a means for providing a precise amount of power from a power source to heat a heating element to a minimum required temperature to completely vaporize a precise volume of a liquid; and b. a means for controlling a precise duration of time to supply the precise amount of power to completely vaporize the predetermined volume of liquid at the required temperature, wherein the precise duration of time or the precise amount of power is adjusted based on a comparison of a temperature of the heating element to the minimum required temperature to completely vaporize the liquid, wherein if the precise volume of liquid is adjusted, the precise duration of time or the precise amount of power is adjusted to completely vaporize the adjusted precise volume of liquid within a new minimum required temperature for a new minimum required time.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161478460P | 2011-04-22 | 2011-04-22 | |
| US61/478,460 | 2011-04-22 | ||
| PCT/IB2012/052044 WO2012120487A2 (en) | 2011-03-09 | 2012-04-23 | Medicant delivery system |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2829043A1 CA2829043A1 (en) | 2012-09-13 |
| CA2829043C true CA2829043C (en) | 2019-09-03 |
Family
ID=49322810
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2829043A Active CA2829043C (en) | 2011-04-22 | 2012-04-23 | Medicant delivery system |
Country Status (3)
| Country | Link |
|---|---|
| JP (2) | JP6187936B2 (en) |
| KR (1) | KR102030512B1 (en) |
| CA (1) | CA2829043C (en) |
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| JP2017127649A (en) | 2017-07-27 |
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| JP6187936B2 (en) | 2017-08-30 |
| KR20140056161A (en) | 2014-05-09 |
| CA2829043A1 (en) | 2012-09-13 |
| JP2014512207A (en) | 2014-05-22 |
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