USRE35552E - Device intended for measuring a dose of powered medicament for inhalation - Google Patents

Device intended for measuring a dose of powered medicament for inhalation Download PDF

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Publication number
USRE35552E
USRE35552E US08/343,930 US34393094A USRE35552E US RE35552 E USRE35552 E US RE35552E US 34393094 A US34393094 A US 34393094A US RE35552 E USRE35552 E US RE35552E
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US
United States
Prior art keywords
shaft
container
medicament
inhalation
dose
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US08/343,930
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English (en)
Inventor
Tapio Lankinen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer Oy
Original Assignee
Leiras Oy
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Publication date
Application filed by Leiras Oy filed Critical Leiras Oy
Priority to US08/343,930 priority Critical patent/USRE35552E/en
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Publication of USRE35552E publication Critical patent/USRE35552E/en
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Classifications

    • 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
    • A61M13/00—Insufflators for therapeutic or disinfectant purposes, i.e. devices for blowing a gas, powder or vapour into the body
    • 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
    • A61M15/0065—Inhalators with dosage or measuring devices
    • 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
    • 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
    • A61M15/0001—Details of inhalators; Constructional features thereof
    • A61M15/0013—Details of inhalators; Constructional features thereof with inhalation check valves
    • A61M15/0015—Details of inhalators; Constructional features thereof with inhalation check valves located upstream of the dispenser, i.e. not traversed by the product
    • 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
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/06—Solids
    • A61M2202/062—Desiccants
    • 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
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/06—Solids
    • A61M2202/064—Powder

Definitions

  • the present invention relates to a section of a powder inhalator required for the inhalation of a powdered medicament, said section containing powdered medicament as well as a mechanism required for measuring its dosage and delivering it out of a reservoir.
  • the dosage of a medicament for inhalation is generally effected by using a propellant-pressurized dosage aerosol or powder inhalator.
  • dosage aerosol the metering of a dose is accurate based on the determination of liquid volume in a dosage valve with external moisture having no effect on the procedure.
  • powder inhalators the metering is inaccurate for several reasons. Measuring or metering a dose is based on two prior known principles.
  • the powder may be contained as measured portions in small dosage containers, e.g. capsules, from which it is metered and delivered into the inhalation air of a patient.
  • a larger amount of powdered medicament can also be contained in a reservoir included in an inhalator, wherein a special mechanism is used for delivering a measured amount of powder into the inhalation air of a patient.
  • a special mechanism is used for delivering a measured amount of powder into the inhalation air of a patient.
  • the medicament doses to be inhaled with powder inhalators may vary within the range of tenths of a milligram to tens of milligrams.
  • the most significant disturbing factor is external moisture . If a powdered medicament is moistened, e.g. during storage, it may form lumps for impaired measuring accuracy.
  • the penetrability of moisture into a medicinal substance depends on the tightness of a medicament reservoir, the water-vapour permeability of a structural material as well as on the moisture absorbency of a medicament itself. It is prior known to alleviate the moisture trouble by means of a dehydrating agent associated with a medicament reservoir.
  • the moistening may be a result of exhalation through an inhalator or of bringing the device from a cold place to a warm one. This moisture trouble could be inhibited by fitting the inhalator with a one-way valve preventing exhalation and other air-flows occurring through the device.
  • a medicament reservoir and a dose measuring mechanism included in a multi-dosage inhalator should fulfil the following conditions:
  • the design of a medicament reservoir and a dose measuring mechanism is highly important not only in terms of dose measuring accuracy and stability of a powdered medicament but also a preferred inhalator structure.
  • No prior art multidosage powder inhalator is provided with a medicament reservoir and a dose measuring mechanism that would fulfil all the above-mentioned conditions.
  • Finnish Patent publication No. 69963 discloses a multidosage dispenser provided with a medicament container and a dose metering device.
  • the medicament container has a conical lower section and its bottom is provided with a shaft rotatable around its longitudinal axis.
  • the shaft is fitted with one or a plurality of dosage recesses, into which the powder is flowing upon rotating said shaft.
  • the container can be fitted with a dehydrating agent and a vibrator for an intensified flow of the powder upon rotating said shaft. After rotating the shaft through half a turn, the dosage recess has rotated so as to reach an inhalation conduit, which is located below the container and into which the powder drops.
  • the powdered medicament is well protected against moisture but it is required to have exceptionally good flowing or trickling properties for a uniform filling of the dosage recess.
  • the medicament container is not replaceable, nor is there provided a one-way valve for blocking exhalation.
  • U.S. Pat. No. 4 046 146 discloses a multi-dosage inhalator, wherein the dose metering is effected by rotating a cylindrical medicament container having a perforated floor.
  • the cylinder rotates around its center axis upon a fixed, circular bottom plate provided with a hole for dropping a dose into an inhalation conduit.
  • the holes in its floor are filled with a powdered medicament and wind up below a plate inside the container in alignment with a hole in the circular bottom plate, wherethrough the powder falls down gravitationally for inhalation.
  • the powdered medicament is poorly protected against moisture due to an extensive, untight sliding surface and a hazard of overdoses is ominous if several loading actions are effected prior to inhalation. Measuring of small doses is obviously inaccurate since gravity alone is not sufficient to cause a complete drop of the dose into an inhalation conduit.
  • the design does not allow for effective use of a one-way valve. However, the medicament container is replaceable.
  • Finnish Patent publication No. 79947 discloses a multi-dosage inhalator, wherein the powder is packed in a medicament reservoir on a perforated sheeting and the perforated point of the sheeting is carried onto an inhalation conduit.
  • the sheeting comprises a thin, circular plastic disc which, upon effecting a loading action, rotates into an inhalation conduit.
  • the medicament reservoir is provided with a dehydrating agent. Despite the dehydrant, moisture will be able to affect the powdered medicament in time by way of wide and extensive sliding surfaces. The action of this device is troubled by a hazard of blocking the holes of a perforated plate and the sticking of medicament to the moist interior walls of an inhalation conduit.
  • the medicament reservoir is not replaceable.
  • the mechanism can be used to measure both small and large amounts of medicament.
  • the question is about a medicament container and a dose measuring mechanism for a multi-dosage powder inhalator for measuring or metering accurately both large and small medicament doses with the powdered medicament permanently and tightly protected from external moisture and for readily facilitating the use of a one-way valve for blocking exhalation through the powder inhalator as well as replaceability.
  • Operation of the device is based on filling a recess in a cross-sectionally circular shaft with an amount equivalent of a single dose of powdered medicament by rotating a shaft-surrounding medicament container around the shaft and in an inhalation conduit adjacent to the dose by pushing the shaft out of the medicament container.
  • Filling of the recess is effected as a result of the gravity-induced powder rolling and by means of a sweeper element, fastened to the medicament container and leaning against the shaft.
  • the sliding surfaces between shaft and medicament container are elastically tight.
  • a device of the invention is characterized in that the container is provided with at least one flap-shaped sweeper element, which rests upon the shaft in alignment with a dosage recess and one of whose ends is rotatable around the shaft, the other end of said flap dragging along the shaft surface, whereafter the shaft is displaceable in its longitudinal direction relative to the container so as to bring the dosage recess along with a medicament dose contained therein to a position below the container.
  • FIG. 1 is a basic view of a device of the invention with a medicament container sectioned in the longitudinal direction of the shaft,
  • FIGS. 2 a, b and c show the device of FIG. 1 in the longitudinal direction of the shaft, wherein the container is turned through a full rotation
  • FIGS. 3 a and b illustrate one embodiment according to the invention
  • FIGS. 4 a and b show an inhalation apparatus including a device of the invention
  • FIG. 5 illustrates another inhalation apparatus provided with a device of the invention
  • FIGS. 6-9 show one modified embodiment of FIG. 5.
  • FIG. 1 the basic structure of a device is shown with a medicament container sectioned in the longitudinal direction of a shaft 3 and FIG. 2 shows it in a cross-section in the direction of the shaft.
  • the device comprises a medicament container housing 1, a gable 2, a circular shaft 3 as well as a flap-shaped sweeper element 4 leaning against the shaft with a slight tension.
  • said shaft 3 is provided with a recess 5 for measuring a dose.
  • a powdered medicament 6 lies freely on the floor of medicament container 1. Inside the container it is possible to place a dehydrating agent 7, packed e.g. as an annular body. Shaft apertures 8 are tight but allow for displacement of the shaft in its longitudinal direction.
  • the number of sweeper elements 4 can also be more than one.
  • the medicament container 1 has preferably a circular cross-section but other shapes are also possible.
  • the shaft 3 is preferably located centrally in the medicament container but can also be located eccentrically.
  • FIGS. 2a, b and c A dose measuring or metering procedure is illustrated in FIGS. 2a, b and c.
  • the powdered medicament first (FIG. 2a) rotates along with the container but, upon continued rotation, it starts to trickle and fall downwards ending up on sweeper element 4 (FIG. 2b).
  • the sweeper element 4 has packed said dosage recess 5 full of powder with a slight tension (FIG. 2c).
  • the dose can be displaced out of the container and simultaneously the tight shaft aperture 8 trims out a possible excess powder.
  • a strong gas flow e.g. induced by inhalation
  • dosage recess 5 the latter is exhausted of the powdered medicament.
  • the term "recess" refers to a depression, located in the shaft and having a volume that matches an individual dose of medicament.
  • Tests have verified that a device provided with a single dosage recess 5 and sweeper element 4 is capable of reaching a measuring accuracy of appr. ⁇ 10% when measuring doses of more than 2 mg.
  • the medicament container 1 can be half-filled with powder and the measuring accuracy begins to deteriorate after appr. 2/3 of the powder has been spent.
  • a cylindrical medicament container 1 having a diameter of 2 cm and a height of 1 cm, is capable of measuring or metering more than 200 doses of 2 mg (depending on the specific gravity of a powder in question).
  • Tests have also verified that the flowing characteristics of certain medicinal formulations are insufficient for an accurate operation of the device. This calls for the use of a mechanism which, in a per se known manner, vibrates the medicament container during rotation.
  • the flowing and the filling of a dosage recess can also be intensified by a special design of the interior container wall as well as by adjusting the length and width of a sweeper element and by an eccentric positioning of shaft 5.
  • a shaft design as shown in FIG. 3, wherein the shaft 3 is hollow at one end slightly beyond said dosage recess 5. Inside the shaft 3 is fitted a stationary tube 9. After dosage recess 5 has been filled, said shaft 3 is pushed out of container 1 while tube 9 retains its position (FIG. 3b). As some of the gas flow (e.g. induced by inhalation) is directed to pass through said tube 9, the dosage recess is effectively exhausted of medicament.
  • the medicament container 1 and the gable with its sweeper element 4 for a device of the invention can be readily manufactured from plastics and the components can be joined together e.g. by press-fitting or ultrasonic welding. If the employed material comprises a suitably elastic material, e.g. soft polyethylene or rather stiff elastomer, no separate shaft sealings 8 are not required. A preferred material for the shaft and its inner tube is polished stainless steel.
  • the filling of a medicinal substance in the container can be effected prior to the attachment of a gable to the container, as one of its shaft apertures is closed, or respectively through the other shaft aperture with the gable in position.
  • a device of the invention can be replaced in the housing of a powder inhalator either without or with a shaft. If a replacement is effected without a shaft, the shaft apertures of a medicament container are protected for the duration of storage by means of a plug, extending through the medicament container and having one of its ends provided with a depression for receiving the shaft end. After removing an empty container from the shaft, the shaft end is placed in this depression and the container is pushed onto the shaft, which forces the plug in front it out of the container. The container will be installed in its proper position according to alignment marks carried therein as well as in the inhalator housing.
  • a device of the invention is capable of measuring at a sufficient accuracy both very small and large amounts of powder.
  • the powdered medicament is extremely well protected from moisture and its design readily facilitates the use of a one-way valve for blocking exhalation through the device. It is easy to manufacture and its replaceability guarantees reasonable maintenance costs.
  • FIG. 4a illustrates a simple device, wherein the passage of a dose into an inhalation conduit 10 is effected by manually pressing a button 11.
  • the shaft comprises a massive shaft as shown in FIG. 1, one of its ends leaning against a socket 13 tensioned by a spring 11.
  • the medicament container is tensioned in its position by means of an annular, spring-equipped gear- mechanism 14, which only allows the rotation of the medicament container in a proper direction and also vibrates the medicament container upon the rotation thereof for a smoother flow of powdered medicament.
  • the shaft is chamfered at 15 in order to maintain its proper position.
  • the example discloses the use of a digital dose counter 16 as well as a contact 17.
  • the container is replaceable by unlocking a clamp unit 18, whereby a section including the container disenegages together with its shaft along a line 19 (FIG. 4b) and the more expensive section, including the dose counter, is in permanent service.
  • a medicament container 1 When using the device, a medicament container 1 is manually turned through one rotation e.g. according to alignment marks, which is followed by pressing in a button 11 and by inhaling through a mouthpiece 20. Upon releasing, the button returns to its original position, whereby the dosage recess pushes itself inside the medicament container is ready for use again.
  • FIG. 5 illustrates a more complicated embodiment, wherein a device of the invention is used for measuring relatively small amounts of powder in association with a vortex chamber pulverizing pharmaceutical particles, as disclosed in Finnish Patent application 892956.
  • the device employs a shaft design as illustrated in FIG. 3. The passage of a dose occurs automatically out of the medicament container and the inhalator is well protected against moistening caused by exhalation.
  • the medicament container has a front cover 2, adapted to serve as the rear wall of a vortex chamber 21.
  • the other gable of the container is provided with two meshings, one 12 being in contact with a gear 24 and the other 23 with a spring 25 mounted on the inhalator housing, the purpose of said spring being to prevent rotation of the container in a wrong direction as well as to vibrate the container during rotation.
  • a shaft 26 carries a reversing wheel 27, a splined cylinder 28 as well as a gear 24 and terminates in a prod 29 for supplying an impulse to a digital dose counter 16.
  • a shaft 3 is fitted with a transfer means 30, one of its ends communicating by way of journalled wheels nearly non-frictionally with the slot of splined cylinder 28 as well as with a rail located below the transfer means and in the bottom section of the inhalator.
  • Exhalation through the device can be done through the dosage recess and tube 9. In practice, however, this is not possible since, when measuring or metering small doses, the hole in the floor of a dosage recess is less than 1 mm in diameter and, thus, a patient does not feel capable of exhaling with a flap valve closing the actual air inlet.
  • the medicament container is replaced by unlocking a hinged portion included in clamp unit 18 and by turning reversing wheel 27 through one rotation.
  • medicament container 1 comes out as pushed by the shaft, whereby it is easy to pull off of shaft 3.
  • a fresh container is installed in position, as described above (page 9).
  • FIGS. 6-9 illustrate one modification to FIG. 5 of an inhalation device provided with a novel metering system.
  • a shaft 3 equipped with a dosage recess 5 remains stationary but, instead, a medicament container 1 and its associated vortex chamber 21 along with its nozzle 20 are movable.
  • a separate section including medicament container 1 is disposed around a fixed shaft 3 provided with dosage recess 5, said shaft penetrating through the medicament container.
  • the open end of the medicament container is provided with a vortex chamber 1 along with its nozzle.
  • a portion of medicament container 1 is provided along its outer wall with a projecting stud, fitting in a spiral slot included in the device.
  • FIG. 6 shows a cross-section along a line A--A in FIG. 6 and FIG. 9 illustrates the device in an opened condition for the replacement of a container for a medicinal substance 1.

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pulmonology (AREA)
  • Biophysics (AREA)
  • Medicinal Preparation (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Catching Or Destruction (AREA)
  • Containers And Packaging Bodies Having A Special Means To Remove Contents (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
US08/343,930 1991-04-15 1991-04-15 Device intended for measuring a dose of powered medicament for inhalation Expired - Lifetime USRE35552E (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US08/343,930 USRE35552E (en) 1991-04-15 1991-04-15 Device intended for measuring a dose of powered medicament for inhalation

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US95574391A 1991-04-15 1991-04-15
US08/343,930 USRE35552E (en) 1991-04-15 1991-04-15 Device intended for measuring a dose of powered medicament for inhalation
PCT/FI1991/000113 WO1992018188A1 (en) 1991-04-15 1991-04-15 Device intended for measuring a dose of powdered medicament for inhalation

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USRE35552E true USRE35552E (en) 1997-07-08

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US07/955,743 Ceased US5295479A (en) 1991-04-15 1991-04-15 Device intended for measuring a dose of powdered medicament for inhalation
US08/343,930 Expired - Lifetime USRE35552E (en) 1991-04-15 1991-04-15 Device intended for measuring a dose of powered medicament for inhalation

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US07/955,743 Ceased US5295479A (en) 1991-04-15 1991-04-15 Device intended for measuring a dose of powdered medicament for inhalation

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US (2) US5295479A (no)
EP (1) EP0533683B1 (no)
KR (1) KR960002186B1 (no)
AT (1) ATE143273T1 (no)
AU (1) AU650873B2 (no)
BR (1) BR9106690A (no)
DE (2) DE4193534T1 (no)
DK (1) DK0533683T3 (no)
ES (1) ES2093702T3 (no)
GR (1) GR3022073T3 (no)
HK (1) HK1006813A1 (no)
LT (1) LT3557B (no)
LV (1) LV10205B (no)
NO (1) NO175136C (no)
RU (1) RU2093197C1 (no)
WO (1) WO1992018188A1 (no)

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US6626171B2 (en) 2000-05-12 2003-09-30 Iep Pharmaceutical Devices Inc. Powder/liquid metering valve
US7185648B1 (en) 1999-10-21 2007-03-06 Paul Kenneth Rand Medicament dispenser
US7461650B1 (en) * 1999-10-21 2008-12-09 Glaxo Group Limited Medicament dispenser
US7862552B2 (en) 2005-05-09 2011-01-04 Boston Scientific Scimed, Inc. Medical devices for treating urological and uterine conditions
US9179691B2 (en) 2007-12-14 2015-11-10 Aerodesigns, Inc. Delivering aerosolizable food products

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US7575761B2 (en) * 2000-06-30 2009-08-18 Novartis Pharma Ag Spray drying process control of drying kinetics
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GB0216562D0 (en) 2002-04-25 2002-08-28 Bradford Particle Design Ltd Particulate materials
US9339459B2 (en) 2003-04-24 2016-05-17 Nektar Therapeutics Particulate materials
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GB0328859D0 (en) * 2003-12-12 2004-01-14 Clinical Designs Ltd Dispenser and counter
BRPI0509348A (pt) * 2004-04-21 2007-09-11 Innovata Biomed Ltd inalador
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GB0425518D0 (en) * 2004-11-19 2004-12-22 Clinical Designs Ltd Substance source
GB0428204D0 (en) 2004-12-23 2005-01-26 Clinical Designs Ltd Medicament container
GB0518400D0 (en) 2005-09-09 2005-10-19 Clinical Designs Ltd Dispenser
WO2009029028A1 (en) * 2007-08-24 2009-03-05 Astrazeneca Ab Breath- triggered inhaler with dose counter
US20090211576A1 (en) * 2007-10-02 2009-08-27 Timo Lehtonen Safety and abuse deterrent improved device
GB0904040D0 (en) 2009-03-10 2009-04-22 Euro Celtique Sa Counter
GB0904059D0 (en) 2009-03-10 2009-04-22 Euro Celtique Sa Counter
JP5720009B2 (ja) 2009-05-18 2015-05-20 アダミス ファーマシューティカルズ コーポレーション ドライパウダー吸入器
KR101716079B1 (ko) * 2016-03-25 2017-03-14 이현희 주방공사를 위한 주방모형활용방법
WO2020148633A1 (en) * 2019-01-14 2020-07-23 Philip Morris Products S.A. Dry powder inhaler

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Cited By (7)

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US7185648B1 (en) 1999-10-21 2007-03-06 Paul Kenneth Rand Medicament dispenser
US7461650B1 (en) * 1999-10-21 2008-12-09 Glaxo Group Limited Medicament dispenser
US20030136406A1 (en) * 1999-12-07 2003-07-24 Kari Seppala Multidose powder inhaler
US6926003B2 (en) * 1999-12-07 2005-08-09 Orion Corporation Multidose powder inhaler
US6626171B2 (en) 2000-05-12 2003-09-30 Iep Pharmaceutical Devices Inc. Powder/liquid metering valve
US7862552B2 (en) 2005-05-09 2011-01-04 Boston Scientific Scimed, Inc. Medical devices for treating urological and uterine conditions
US9179691B2 (en) 2007-12-14 2015-11-10 Aerodesigns, Inc. Delivering aerosolizable food products

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AU650873B2 (en) 1994-07-07
US5295479A (en) 1994-03-22
WO1992018188A1 (en) 1992-10-29
GR3022073T3 (en) 1997-03-31
HK1006813A1 (en) 1999-03-19
NO924730L (no) 1992-12-08
DK0533683T3 (da) 1997-01-13
KR960002186B1 (ko) 1996-02-13
DE69122388T2 (de) 1997-03-27
LV10205A (lv) 1994-10-20
EP0533683A1 (en) 1993-03-31
RU2093197C1 (ru) 1997-10-20
KR930700175A (ko) 1993-03-13
AU7663291A (en) 1992-11-17
LT3557B (en) 1995-12-27
NO175136B (no) 1994-05-30
EP0533683B1 (en) 1996-09-25
DE69122388D1 (de) 1996-10-31
DE4193534T1 (de) 1997-07-24
ES2093702T3 (es) 1997-01-01
LV10205B (en) 1995-06-20
NO924730D0 (no) 1992-12-08
NO175136C (no) 1994-09-07
LTIP929A (en) 1995-03-27
BR9106690A (pt) 1993-06-29
ATE143273T1 (de) 1996-10-15

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