巴西专利BR112012017177B1 aerosolization system

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专利摘要:
AEROSOLIZATION SYSTEM. An aerosolization system includes a compressible container having a resilient container body. The container configured to dispense the unit dosage of a liquid when compressed only once. The system also includes an aerosolizer that is constructed of a housing that defines a nozzle and an aerosol generator arranged in the housing. The aerosol generator comprises a vibrating membrane having a front face and a rear face and a vibrating element used to vibrate the membrane. In addition, the housing includes an opening which is adapted to receive a unit dosage of the liquid in the container. The opening provides a liquid path to the rear face of the vibrating membrane.
公开号:BR112012017177B1
申请号:R112012017177-1
申请日:2011-01-12
公开日:2020-10-13
发明作者:John S. Patton；Ryan S. Patton；Mei-chang Kuo；Yehuda Ivri
申请人:Dance Pharmaceuticals Inc；
IPC主号:

专利说明:

CROSS REFERENCES WITH RELATED ORDERS
[1] This order claims the priority of US order No. Serial 13 / 004,662 filed on January 11, 2011 which is a continuation, in part, of the order priority and claims of US Provisional Order No. 61 / 335,769, filed on January 12, 2010, the full description of which is incorporated herein by reference.
[2] This order is also related to copending US Order No. 13 / 004,645 filed on January 11, 2011, entitled “Preservative Free Insulin Formulations and Systems and Methods for Aerosolizing” and filed on the same date as this application, whose full description is incorporated here by reference. FIELD OF THE INVENTION
[3] This invention, in general, relates to a single dose inhaler and insulin-forming containers. The inhaler dispenses aerosolized pharmaceutical agents for dispensing drugs by local or systemic inhalation to the lungs. The invention is particularly, but not exclusively, useful for dispensing free doses of insulin preservatives for the treatment of type I and / or type II diabetic patients. BACKGROUND OF THE INVENTION
[4] There are several types of inhalers to aerosolize liquids. For example, US Patent No. 5,586,550, incorporated herein by reference, describes an inhaler that comprises a dispersing mechanism in which a membrane with tapered openings is vibrated such that liquid in contact with a rear membrane surface is dispensed from of a front face of the membrane as an aerosol.
[5] While effective in nebulizing liquids, such inhalers may not be particularly adapted for certain applications, such as unit doses of aerosolization of insulin for pulmonary dispensing.
[6] Consequently, the invention provides inhalers for dispensing doses in a repeatable and predictable manner. As described below, inhalers of the invention may find particular use in aerosolizing liquid insulin for pulmonary dispensing. BRIEF SUMMARY OF THE INVENTION
[7] The invention provides several aerosolization systems, including containers for supplying liquid to inhalers, as well as methods for their use. In an exemplary embodiment, the invention provides an aerosolization system that comprises a compressible container having a resilient container body. The container is configured to dispense the unit dosage of a liquid when compressed only once.
[8] The system also includes an aerosolizer comprising a housing that defines a nozzle and an aerosol generator arranged in the housing. The aerosol generator comprises a vibrating membrane having a front face and a rear face and a vibrating element used to vibrate the membrane. In addition, the housing includes an opening which is adapted to receive a unit dosage of the liquid in the container. The opening provides a liquid path to the rear face of the vibrating membrane.
[9] In one aspect, the aerosolizer includes a hollow needle that is configured to pierce the compressible container and deliver the liquid to the rear face of the vibrating membrane. Also, the compressible container may comprise a single unit dose blister. For example, the blister may comprise the blow-filled sealing container that contains a preservative-free solution. The bubble may additionally comprise a compressible body containing the solution, the upper part removed by rotation and a flap adapted to present information about the solution.
[10] In another aspect, the single unit dose has a concentration in the range of about 200 units of insulin ("IU") / ml to about 800 IU / ml.
[11] In one embodiment, the container comprises a bottle containing the volume of the liquid. In one aspect, the bottle may include a metering valve that allows a discrete droplet of liquid to be dispensed each time the bottle is compressed. In other cases, the droplet size can be controlled, at least in part, on the diameter of the tip of the bottle and the viscosity of the liquid.
[12] The invention additionally provides another aerosolization system comprising a container in the form of an ampoule containing a capillary that maintains a single unit dose of a liquid. The system also includes an aerosolizer comprising a housing that defines a nozzle and an aerosol generator arranged in the housing. The aerosol generator comprises a vibrating membrane having a front face and a rear face and a vibrating element used to vibrate the membrane. Also, the housing includes an opening that is adapted to receive a unit dose of liquid from the container. In addition, the opening provides a liquid path to the rear face of the vibrating membrane.
[13] In a particular aspect, the ampoule additionally comprises a rupture-removed upper part and a ruptured lower part. The capillary is dimensioned in such a way that the surface tension in the capillary prevents the liquid from leaking after removing the upper part but before removing the lower part.
[14] A further embodiment of the invention provides an aerosolization system having a container comprising a container body that maintains a liquid supply and a plunger device that is mobile to dispense a single unit dose of a liquid from the container when operating the plunger device at a fixed distance. An aerosolizer comprises a housing that defines a nozzle and an aerosol generator arranged in the housing. The aerosol generator comprises a vibrating membrane having a front face and a rear face and a vibrating element used to vibrate the membrane. In addition, the housing includes an opening which is adapted to receive a unit dosage of the liquid in the container. The opening provides a liquid path to the rear face of the vibrating membrane.
[15] In one aspect, the container additionally includes a measuring device that is rotated to control the movement of the plunger in order to adjust a single unit dose amount. BRIEF DESCRIPTION OF THE DRAWINGS
[16] Fig. 1 is a partial cross-sectional perspective view of an embodiment of a dispersible mechanism and compressible container according to the claim.
[17] Fig. 2 is a more detailed view of the dispersing mechanism and container of Fig. 1.
[18] Fig. 3 illustrates the dispensing device of Fig. 1, which shows a more detailed view of a base for holding the container and a needle for delivering dispensed liquid to an aerosol generator.
[19] Fig-4 is a perspective view of another embodiment of a dispersing mechanism and a compressible bottle according to the claim.
[20] Fig. 5 illustrates another embodiment of a container for dispensing a unit volume of a liquid according to the claim.
[21] Fig- 6 illustrates the container of Fig. 5 when a unit volume of liquid is dispensed in the dispersing mechanism of Fig. 4.
[22] Fig-2 illustrates an embodiment of an ampoule for dispensing a unit volume of a liquid according to the claim.
[23] Fig. 8 shows the bulb in Figure 7 with one end removed.
[24] The pig. 9 illustrates the ampoule of Fig. 8 with the upper end also removed and being deposited in a dispersing mechanism.
[25] Fig. 10 illustrates another embodiment of a container for dispensing a unit volume of liquid in the dispersing mechanism of Fig. 4. DETAILED DESCRIPTION OF THE INVENTION
[26] Certain aspects of the invention describe an aerosolization mechanism that comprises a housing that defines a dispensing outlet, a vibrating membrane having a front face exposed at the outlet and a rear face to receive a liquid to be dispensed and a vibrating mechanism connected to the housing and operable to vibrate the membrane to dispense aerosol from the liquid across the membrane. A liquid dispensing system is used to dispense a measured amount of liquid from the back face of the membrane. In this way, a measured amount of liquid is dispensable at the outlet by operating the vibrating mechanism for a period of operation sufficient to completely aerosolize the measured amount of the rear face.
[27] An advantage of such a mechanism is that it facilitates the dispensing of substantially all of the liquid that comes in contact with the back face of the membrane as a single dose, especially when the measured dose is relatively small in volume. By dispensing the full dose, the membrane is essentially free of liquid from one dose to follow. In this way, it is possible to avoid contact between the liquid and the ambient air during periods of non-use between successive uses. For pharmaceutical preparations, it is particularly important, as this can obviate the need for the use of preservatives in the liquid and prevents evaporative losses. For example, several preservative-free insulin formulations that can be used include those described in copending US Order No. 13 / 004,645, entitled “Preservative Free Insulin Formulations and Systems and Methods for Aerosolizing” and filed on the same date as the present application, previously incorporated by reference.
[28] The liquid delivery system, in one embodiment, may comprise a deformable thin-walled blister containing a pharmaceutical agent. The delivery system further comprises a mechanical press configured to deform the thin-walled bubble such that a single, preservative-free unit dose is dispensed. The compression mechanism is provided with a dispensing station provided with an operable puncture needle to puncture the bubble and release its contents on performance.
[29] In one aspect, the needle has two ends, with the first end protruding from the surface of the dispensing station and a second end extending from the rear face of the aerosol generator. In use, the bubble is placed in the dispensing station and the pressure mechanism forces the bubble towards the needle that punctures through the thin wall. In this way, the needle provides a conduit for moving the liquid from the bubble to the rear face of the vibrating membrane. When the pressure mechanism is released, the bubble expands and returns to its natural position. The expansion creates a suction action that removes liquid from the needle and prevents drying and clogging.
[30] In another aspect, the bubble has a bellows geometry that can expand and compress elasticly. The term expand and compress in an elastic way includes when the bubble is fully compressed, the internal stresses are still within the elastic range of the material in use, in this way, the bubble can return to its natural position when the pressure mechanism is released. In a particular aspect, the pharmaceutical agent fills at least 80% of the internal volume of the blister and more preferably more than 90% of the volume. This prevents the movement of the liquid, which in some cases can cause the composition to aggregate.
[31] Conveniently, the tip of the needle can be positioned close to the rear face of the vibrating membrane. In addition, the housing can define a duct that communicates between an air inlet and an outlet port. The dispensing outlet is located in the intermediate duct to the air inlet and to the outlet port such that the front face of the membrane is exposed to the air inside the duct. The outlet port can be a mouthpiece for inhalation or an adapter for nasal use.
[32] Such a provision is particularly useful in the administration of inhaled pharmaceutical liquid products when a fine liquid aerosol is required to be in a stream of inhaled air that passes through the nozzle. An example of such a liquid is an insulin composition.
[33] Referring now to Fig. 1, an embodiment of an inhaler will be described. Fig. 1 illustrates a partial cutting path of the single dose inhaler 100 and a unit dose blister package 201 to deliver a metered amount of insulin to the inhaler. Inhaler 100 comprises two subassemblies 102 and 112. The first subassembly 102 defines a compartment for the electronic circuit and batteries and the second assembly 112 defines a housing with a dispensing outlet 105 and contains a vibrating membrane aerosol generator 108 and a dispensing mechanism. 104.
[34] Aerosol generator 108 has a front face exposed in the outlet duct 111 and a rear face 109 contacted in use by the liquid to be dispensed. The aerosol generator 108 is connected to the subassembly housing 112 and is operable to dispense the active pharmaceutical agent as an aerosol through the nozzle 105. Exemplary aerosol generators that can be used are also described in U.S. Patent No. 5164740; 6629646; 6926208; 7108197; 5938117; 6540153; 6540154; 7040549; 6921020; 7083112; 7628339; 5586550; 5758637; 6085740; 6467476; 6640804; 7174888; 6014970; 6205999; 6755189; 6427682; 6814071; 7066398; 6978941; 7100600; 7032590; 7195011, incorporated herein by reference. These references describe exemplary aerosol generators, ways of making such aerosol generators and ways of delivering liquid to aerosol generators and are incorporated by reference at least for these characteristics. Aerosol generators may comprise vibrating membranes having a conical opening with a size in the range of about 3 pm to about 8 pm, preferably from about 3 pm to about 6 pm and in some cases around 4 pm. The membrane can be dome-shaped and vibrated by an annular piezoelectric element that circumscribes the openings. The diameter of the membrane can be in the range of about 5 mm to about 8 mm. The membrane can also have a thickness in the range of about 50 microns to about 70 microns. Typically, the membrane will be vibrated at a frequency in the range of about 50 kHz to about 150 kHz.
[35] Each time the dispensing system is operated it dispenses a measured amount of the liquid from the unit dose bubble 201 to the rear face 109 of the aerosol generator. Since, for each use, a measured amount of the aerosolized pharmaceutical agent is dispensed at the nozzle outlet 105 by the operation of the aerosol generator.
[36] Blister 201 contains a predetermined volume of an active pharmaceutical agent to be dispensed. In one embodiment, blister 201 contains about 80 to about 120 microliters of insulin. The lower limit is typically at least about 15 microliters and the upper limit is typically about 1,000 microliters to about 2,000 microliters. A particularly useful range is about 80 microliters to about 120 microliters at a concentration of about 100 insulin units / ml or more and more preferably about 200-800 units / ml and in some cases as high as 2,500 units / ml ml. Bubble 201 is made of deformable thin-walled material. Due to the sensitivity of insulin to mechanical agitation, the 201 bubble is filled to almost full volume. Specifically, more than 80% of the volume is filled with insulin.
[37] Inhaler 100 additionally includes a dispersion station configured to dispense the contents of the bubble 201 to the aerosol generator 108. The dispensing station includes a rotating arm member 104 and a bubble base 107. The bubble base 107 has a concave shape that can radially join the convex shape of the bubble 201. The bubble base 107 additionally includes a hypodermic needle 112 that establishes a fluid passage from the bubble to the vibration of the aerosol generator 108. The needle 112 has two sections . The first section 112A extends from the dispensing base and protrudes externally perpendicular to the bubble base 107. The second end 112B extends internally towards the aerosol generator 108 and is positioned close to the rear face of the vibration membrane of the aerosol generator 108. Typically, second end 112B will be less than 5 mm and more preferably less than 2 mm from the vibration membrane of the aerosol generator 108. The hypodermic needle 112 can be made of alloy steel type 316 stainless steel with a measurement size ranging from measurement 22 to measurement 26. The first section 112A has a sharp inclined drill bit. In use, the bubble 201 is placed on the concave base 107 and then a rotating arm 104 is rotated in the opposite direction in the direction of the arrow 115.
[38] Conveniently, the force on the rotating arm 104 can be applied by a finger against the curved portion of the arm 104. This action forces the bubble toward the needle tip of needle 112A which subsequently pierces the bubble 201 and compresses its contents by through a needle 112 through the needle outlet 112B and in the aerosol generator 108. When the rotating arm 104 is fully lowered, the total dosage is dispensed to the vibration membrane of the aerosol generator 108.
[39] Fig. 2 illustrates the vibration membrane 109 of the aerosol generator 108 in more detail. When the contents of the blister 201 are completely dispensed, an indicator light 120 begins to flash to signal the patient that the inhaler 100 is ready for use. In any shorter time, therefore, the patient can inhale through the nozzle 105. The patient's inhalation is detected by a flow sensor that is rotated to activate the aerosol generator 108 to produce the aerosol particles in the 111.0 aerosol duct is placed in the inhalation airflow in the direction shown by arrows 121 and flow through the respiratory system to the patient's lungs. When the total dosage is aerosolized, which can take one or more breaths, the “end of dose” indicator light 121 comes on a second time to signal the patient that the total dosage has been dispensed. The dispensing of a total dosage is achieved when at least about 95% of the dose is dispensed, more preferably 98% and most preferably when more than 99% of the dose is dispensed. In one embodiment, the opening funnel for the aerosol generator is large enough that the dispensing of liquid to the aerosol generator is dispensed in its entirety. To receive the dose, the patient can take several inhalations or a single inhalation depending on the volume delivered to the network and the patient's breathing capacity. Each inhalation should be a deep breath to ensure that the aerosol reaches the lungs deeply.
[40] When the end of dose indicator light 120 is activated following inhalation of the contents of blister 201, the empty blister can be removed and discarded. When the finger pressure on the rotating arm 104 is released, the bubble expands to its original shape. The expansion creates a vacuum inside the bubble 201 that draws any fluid adhered from a needle back to the bubble, thereby leaving the inside of the needle dry to prevent drying and clogging of material. In order to avoid possible bacterial contamination, the internal and / or external surfaces of the needle, the needle 112 can be coated with silver, a silver based coating or the like.
[41] Fig. 3 illustrates the concave base 107 of the dispensing station in more detail. Base 107 is provided with holes 117 that provide access to the interior of the inhaler in the vicinity of aerosol generator 108. This allows solvent cleaning and water rinsing to be provided to aerosol generator 108.
[42] Fig. 4 provides an alternative dispensing system for an inhaler 500 that uses a preservative-free dispenser 550 and a nozzle 551 to deliver a volume of preservative-free pharmaceutical agent to the aerosol generator through an opening 501. Inhaler 500 may be constructed in a similar manner to inhaler 100 and may include a similar aerosol generator. The opening 501 has a funnel shape that tapers to a small opening 502, thus forming a slope 503. The dispenser 550 is a uniform drop, the preservative-free dispenser which, upon activation, replaces a single drop through the tip of its spout 551. Preferably, the droplet volume is less than about 200 microliters. The dose is dispensed by compressing the container 550 in a direction perpendicular to its longitudinal axis. In each actuation, a single drop of a fixed volume is displaced through the nozzle 551.
[43] An exemplary dispenser is the Aptar OSD dispenser, developed by Ing. Erich Pfeiffer GmbH. Such a container is constructed from a compression bottle that is compressed to dispense a droplet. When released, the nozzle prevents microbiological contaminants from entering the remaining liquid. This is done through a seal at the tip that prevents liquid from refluxing into the container. The tip sealing mechanism includes a spring that holds the tip seal in place in a normally closed position. When the bottle is compressed, the liquid passes between the seal and a cap until sufficient pressure is created to overcome the spring force. In this way, a single droplet can be dispensed. After dispensing, the tip seal closes again preventing the liquid from moving back into the container. To relieve the accumulation of vacuum inside the bottle, a small hole is included in the face of the container to allow air in the spring chamber. The droplet size can be controlled based on several factors including the size of the top and the viscosity of the liquid.
[44] In use, the nozzle 551 is aligned with the opening 501 such that the upper part is dispensed with the slope 503 and flows through the opening 502 to the aerosol generator. Preferably, the angle of inclination 503 is greater than about 30 degrees with respect to the axis of aperture 502. Opening diameter 501 is about 10 mm to about 15 mm and opening diameter 502 is at least about 5 mm. The pharmaceutical fluid in the preservative-free dispenser 550 may be contained in an articulated bag to prevent excessive agitation and which can be damaged by mechanical movement. For example, proteins, such as insulin, can be sensitive to mechanical agitation. The use of an articulating bag can limit undesirable agitation.
[45] In another embodiment, instead of using a container of the type described in Fig. 5, a container 600 can be used. Container 600 comprises a bubble 602 manufactured using a blow-filled sealing process. Container 600 is similar to container 201 of Fig. 1 in which when the bubble 602 is compressed an amount of unit dosage is dispensed.
[46] The blister 602 comprises a compressible body 604 having a flap 606 and an upper part removed by rotation 608. The body 604 is sized to maintain a unit dosage of liquid and the flap 606 can include various types of identification information, such as such as batch number, date and others. The rotationally removed upper part 608 provides an easy way for the bubble to open 602 so that liquid can be dispensed.
[47] Also referring to Fig. 6, the use of blister 602 in delivering a unit dose of liquid to the inhaler 500 will be. When ready to receive a treatment, the user takes the bubble 602 and removes the cap by rotating it 608. Typically, the bubble 602 will be kept in an upright position so that no liquid escapes. In some cases, the opening formed when the upper part 608 is removed may be small enough to prevent the liquid from escaping. Bubble 602 is moved over opening 501 and body 604 is compressed to expel the complete volume of liquid 610 in opening 501 where the liquid drains through opening 503 and the aerosolizer. In this way, blister 602 functions as a hand-compressible, single-use container for the preservative-free solution. The use of a blow-filled sealing process is particularly advantageous in that the bubble 602 can be manufactured at low cost while additionally allowing the preservative-free solution to be stored. Also, the measurement process is simple, requiring only the removal and compression of the bubble.
[48] Fig. 7 illustrates an embodiment of an ampoule 700 for dispensing a unit volume of a liquid to be aerosolized. The ampoule 700 comprises an elongated body 702 defining a capillary that maintains a unit volume of liquid 704. The ampoule 700 additionally includes an upper end 706 and a lower end 708 which can be removed from the body 702, such as by removing it by rupture. The body 702 can generally be constructed of a rigid material that is sufficiently stiff to allow the two ends to be easily removed by rupture.
[49] When ready to dispense the liquid in an inhaler, the upper end 706 is removed as shown in Fig. 8. The surface tension in the body 702 prevents the leakage of any liquid 704 when the ampoule 700 is inverted as when inserting the ampoule 700 in an inhaler.
[50] Fig. 9 illustrates an ampoule from Fig. 8 after being inserted into an inhaler 720. The inhaler 720 can be constructed in a similar manner to the other embodiments described here and includes electronics 722 that are used to control the operation of an aerosol generator 724 having a vibrating network 726. The inhaler 720 includes an elongate opening 730 into which the ampoule 700 is inserted after the end 706 is removed. Once in place, end 708 is removed by rupture allowing the liquid 704 to drain from the ampoule 700 and on the rear face of the vibrating mesh 726 as illustrated in Fig. 9. When the mesh 726 vibrates, the liquid is aerosolized and directed to the nozzle 732 where the patient can inhale the drug. Following aerosolization, ampoule 700 can be removed from inhaler 720 and discarded.
[51] Fig. 10 illustrates another embodiment of a container 800 for dispensing a unit volume of liquid in the dispersing mechanism 500 that was previously described in connection with Fig. 4. Container 800 comprises a container body 802 which defines a reservoir 804 to maintain a volume of liquid to be dispensed. A plunger 806 is used to force liquid in reservoir 804 through a dispensing end 808 of container 800. Container 800 also includes a gear measuring mechanism 812 that is rotated or “adjusted” to control the extent of movement of the plunger 806.
[52] In addition, an actuator 814 is compressed to move the plunger 806 by the amount allowed by the measuring mechanism 812. In this way, a user can simply “adjust a dose” of liquid using an 812 measuring mechanism and then press the actuator 814 in order to dispense a measured amount of liquid in the orifice 501 where it will be supplied to the aerosolization mechanism.
[53] Container 800 can be configured to be disposable or reusable. When reusable, reservoir 804 can comprise a cartridge that is inserted into the space defined by reservoir 804. Exemplary volume sizes can be about 1, 1.8 or 3 ml cartridges, which can be made of glass, LDPE or similar.
[54] The invention has now been described for the purposes of clarity and understanding. However, it will be estimated that certain changes and modifications may be practiced within the scope of the attached claims.

权利要求:
Claims (7)
[0001]
1. Aerosolization system, characterized by the fact that it comprises: a container (201, 550, 600, 700, 800) comprising a container body (802), the container being configured to dispense a single uniform drop of liquid when actuated, the container comprising a spout (551) having a tip with a seal at the tip which prevents reflux of liquid in the container; an aerosolizer comprising: a housing that defines a nozzle (105, 732); an aerosol generator (108, 724) arranged entirely within the housing, wherein the aerosol generator comprises a vibrating membrane (109) having a front face and a rear face and a vibrating element used to vibrate the membrane (109); wherein the housing includes an opening (501, 502, 730) which is adapted to receive a dose of liquid from the container while the container is generally external to the housing, so that the container can be pressed by a human hand to manually actuate the container while the container is out of the housing, where the opening provides a liquid path configured to drain the full dose to the rear face of the vibrating membrane, where the dose is stored on the rear face until the vibrating element is energized to aerosolize the dose complete stored on the rear face.
[0002]
2. Aerosolization system according to claim 1, characterized by the fact that the liquid has a concentration in the range of 200 IU / ml to 800 IU / ml.
[0003]
Aerosolization system according to claim 1, characterized in that the container (550) comprises a bottle containing the volume of the liquid and in which the bottle is configured to dispense a discrete droplet of the liquid of a certain volume when the bottle is compressed.
[0004]
Aerosolization system according to claim 1, characterized by the fact that: the container (201, 550, 600, 700, 800) comprises an ampoule (700) containing a capillary that maintains a single unit dose of a liquid; wherein the housing includes a well-sloped region (503) that drains into the opening.
[0005]
5. Aerosolization system according to claim 4, characterized by the fact that the inclined region has a diameter of 10 mm to 15 mm.
[0006]
6. Aerosolization system according to claim 1, characterized by the fact that it additionally comprises: a spring that maintains the tip seal in a normally closed position, in which the actuation of the container creates sufficient pressure to move the tip seal and to dispense the dose of liquid from the nozzle, and where after dispensing, the tip seal closes to prevent the liquid from returning to the container.
[0007]
Aerosolization system according to claim 6, characterized by the fact that an opening (501) comprises a circular orifice (502), and in which a well inclined region (503) is formed by the housing.

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法律状态:
2019-01-08| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

2019-07-30| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

2020-02-27| B07A| Application suspended after technical examination (opinion) [chapter 7.1 patent gazette]|

2020-07-28| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

2020-10-13| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 12/01/2011, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

申请号 | 申请日 | 专利标题

US33576910P| true| 2010-01-12|2010-01-12|

US61/335769|2010-01-12|

US13/004,662|US8950394B2|2010-01-12|2011-01-11|Preservative-free single dose inhaler systems|

US13/004662|2011-01-11|

PCT/US2011/020925|WO2011088070A1|2010-01-12|2011-01-12|Preservative-free single dose inhaler systems|

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