DK152967B - INHALATOR FOR DELIVERING SIMPLE POWDER DOSES - Google Patents
INHALATOR FOR DELIVERING SIMPLE POWDER DOSES Download PDFInfo
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- DK152967B DK152967B DK343874AA DK343874A DK152967B DK 152967 B DK152967 B DK 152967B DK 343874A A DK343874A A DK 343874AA DK 343874 A DK343874 A DK 343874A DK 152967 B DK152967 B DK 152967B
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- chamber
- container
- flange
- aerosol
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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
- A61M15/00—Inhalators
- A61M15/0086—Inhalation chambers
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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
- A61M15/00—Inhalators
- A61M15/009—Inhalators using medicine packages with incorporated spraying means, e.g. aerosol cans
-
- 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
Description
, DK 152967 B, DK 152967 B
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Opfindelsen angår en inhalator til afgivelse af ensartede doser af et i et drivmiddel suspenderet medikamentpulver ved lav hastighed i form af en inhaler-bar tør aerosol med partikelstørrelser fra 0,5 til 10 pn.The invention relates to an inhaler for delivering uniform doses of a low-speed drug powder suspended in a propellant in the form of an inhalable dry aerosol of particle sizes from 0.5 to 10 µm.
5 Inhalation af medikamenter har længe været kendt. Der arbejdes dog fortsat på at sikre tilvejebringelse af ensartede, forholdsvis nøjagtigt afmålte doser af suspenderede partikler inden for bestemte størrelsesområder. Større partikler har nemlig tendens til at afsættes 10 i munden og halsens øverste del, medens mindre partikler på under ca. 10 pn vil trænge dybere ned og nå frem til lungerne. Det er derfor et problem at sikre afgivelsen af et ønsket medikament i en ønsket dosis med et ønsket størrelsesområde til et ønsket tidspunkt. Ofte har et 15 medikament systemisk virkning på andre organer end det tilsigtede, og denne virkning er faktisk uønsket. F.eks. har mange steroider både systemisk virkning, hvis de indgives oralt, og lokal virkning på lungerne selv. Det er derfor ønskeligt ved visse terapeutiske behandlinger at 20 indgive steroiderne kun til lungernes overflader, dvs. i så vidt omfang som muligt at sikre mod afsætning i mundhulen og svælget.5 Inhalation of drugs has long been known. However, work is continuing to ensure the provision of uniform, relatively accurately metered doses of suspended particles within specific size ranges. Larger particles tend to deposit 10 in the mouth and upper part of the throat, while smaller particles of less than approx. 10 pn will penetrate deeper and reach the lungs. Therefore, it is a problem to ensure the delivery of a desired drug at a desired dose with a desired size range to a desired time. Often, a drug has a systemic effect on organs other than the intended, and this effect is actually undesirable. Eg. Many steroids have both a systemic effect if administered orally and a local effect on the lungs themselves. It is therefore desirable in certain therapeutic treatments to administer the steroids only to the surfaces of the lungs, ie. as far as possible to ensure against sales in the oral cavity and pharynx.
Fra britisk patentskrift nr. 830.427 kendes en aerosoldispenser forsynet med en decellerator i form af 25 et rør, der kan have en maksimal indvendig diameter beliggende i området 6-32 mm og en længde beliggende i området 70-102 mm.British Patent Specification No. 830,427 discloses an aerosol dispenser provided with a deceller in the form of a tube which may have a maximum internal diameter in the range of 6-32 mm and a length located in the range of 70-102 mm.
Det har nu vist sig, at udtømningen fra en aerosolbeholder kan suspenderes i et tørt fordampet drivmid-30 del blandet med luft ved anvendelse af et decellerations-kammer, der er stort nok til at tjene som bærer for aerosolbeholderen i den stilling, der benyttes ved opbevaring og transport, og som ved sin ene ende er indsnævret til etmundstykke og ved sin anden ende er indsnævret til et 35 sprøjtesystem, og dette opnås ved inhalatoren ifølge op-It has now been found that the discharge from an aerosol container can be suspended in a dry vaporized propellant mixed with air using a deceleration chamber large enough to serve as a carrier for the aerosol container in the position used at storage and transport, which at one end is narrowed to a nozzle and at its other end is narrowed to a syringe system, and this is achieved by the inhaler according to the invention.
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findelsen, der er ejendommelig ved, at den omfatter en cirkulærcylindrisk aerosolbeholder og et decellera-tionskammer, hvilken aerosolbeholder er forsynet med en doseringsventil og indeholder medikamentpulveret 5 suspenderet i drivmidlet, og hvilket decellerationskam-mer i det væsentlige består af en cylindrisk tønde med en længde på under to gange dens diameter, fortrinsvis en længde på ca. 7 cm og en indvendig diameter på ca. 4 cm, med et ved den ene ende anbragt cylindrisk mundstykke, 10 der har en overgang til decellerationskammeret, hvilket mundstykke med en ydre diameter på fortrinsvis ca. 2 cm og en længde på fortrinsvis ca. 1,5 cm er indrettet til at passe i et menneskes mund og er anbragt koaksialt med den cylindriske tønde ved hjælp af overgangen, og er for-15 synet med en aftagelig mundstykkekapsel til nøje sammenpasning med og lukning af mundstykket i støvtæt sammenhæng, og med en ved den anden ende af kammeret monteret aftagelig beholderholder indrettet til at slutte praktisk taget lufttæt til decellerationskammeret og omfattende 20 en beholderflange indrettet til at passe tæt med kammerets cylindriske tønde og en med flangen koaksial knap-holder, der er hul, men lukket i den over for flangen liggende ende og har en rund monteringsåbning til indstikning og fiksering i én bestemt retning af en på dose-25 ringsventilen anbragt, cylindrisk udløserknap, der er forsynet med en på tværs udboret sprøjteåbning forbundet med en på langs udboret kanal forbundet med doseringsventilens afgangsåbning, idet åbningen er afrettet fladt på den mod flangen vendende side, der passer sammen med en på udlø-30 serknappen indrettet flad side, hvor sprøjteåbningen udmunder med retning fremad mod decellerationskammeret, hvilket tillader udtømning af aerosolbeholderen aksialt i decellerationskammeret, når udløserknappen og aerosolbeholderen indbyrdes befinder sig i doseringsstilling under 35 afgivelse af en aerosolstrøm, hvorhos der findes en på flangen koaksialt med denne anbragt og fortrinsvis trinvis aftrappetthe invention, characterized in that it comprises a circular cylindrical aerosol container and a deceleration chamber, which is provided with a metering valve and contains the drug powder 5 suspended in the propellant, and which essentially consists of a cylindrical barrel of a cylindrical barrel. less than twice its diameter, preferably a length of approx. 7 cm and an inside diameter of approx. 4 cm, with a cylindrical mouthpiece disposed at one end, 10 having a transition to the deceleration chamber, said mouthpiece having an outer diameter of preferably about 10 cm. 2 cm and a length of preferably approx. 1.5 cm is arranged to fit in a human's mouth and is arranged coaxially with the cylindrical barrel by means of the transition, and is provided with a removable mouthpiece capsule for close mating and closure of the mouthpiece in a dustproof context, and with a removable container holder mounted at the other end of the chamber adapted to connect practically airtight to the deceleration chamber and comprising a container flange adapted to fit snugly with the cylindrical barrel of the chamber and a flange coaxial button holder which is hollow but closed therein. opposite the flange and has a round mounting opening for insertion and fixation in one particular direction of a cylindrical release button provided on the metering valve, which is provided with a transversely bore syringe opening connected to a longitudinal bore channel connected to the outlet opening of the metering valve. , the aperture being flattened flat on the flange-facing side that matches a p the flat button exits the flush side, wherein the syringe opening opens in a forward direction towards the deceleration chamber, which permits the discharge of the aerosol container axially into the deceleration chamber, when the release button and the aerosol container are mutually in a dosing position during delivery of an aerosol stream therein, with this disposed and preferably stepwise
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tragt, der tjener som afskærmende dyse til at rette sprøjtestrømmen aksialt ind i decellerationskammeret.funnel which serves as a shielding nozzle to direct the spray flow axially into the deceleration chamber.
I modsætning til det, som angives om afsætning af medikament i en decellerator ifølge britisk 5 patent nr. 830.427, hvor man netop ønsker at undgå medikament afsat på væggene, kan man med inhalatoren ifølge opfindelsen acceptere afsætning i endog ganske betydeligt omfang på 25 til 50% på kammerets vægge, når blot dette omfang er konstant fra den ene dosering til den næste.Contrary to what is stated about the dispensing of a drug in a decelerator according to British Patent No. 830,427, where it is precisely desired to avoid the drug deposited on the walls, the dispensing of the inhaler according to the invention can accept even to a considerable extent of 25 to 50 % on the walls of the chamber, provided that this extent is constant from one dosage to the next.
10 Decellerationskammeret har nogenlunde samme rumfang som menneskets mundhule, når munden står åben.10 The deceleration chamber has approximately the same volume as the human oral cavity when the mouth is open.
Det tjener til at decellerere en afgiven portion af aerosol til levering af det dispergerede pulver med lav hastighed, til at optage aerosolstrømmens bevægelsesmoment, 15 før det suspenderede pulver indtræder i brugerens mund, til at fuldstændiggøre aerosoldrivmidlets fordampning, til at eliminere muligheden for, at flydende drivmiddel når munden, til at fortynde drivmidlet og suspenderet pulver med luft og til at tilvejebringe ensartede og 20 acceptable pulvertab, således at der indgives ensartede doser. Det er ønskeligt, at en hovedportion af et udtømt eller afgivet medikament indtages af brugeren, men det er vigtigere, at hver enkelt dosis har overensstemmende og forudsigelig størrelse og absorberbarhed, således at en 25 kendt ensartet dosis indgives ved hver påvirkning eller udløsning af udløserknappen. En anselig tabsprocent kan accepteres, hvis den er pålideligt ensartet. Med det foreliggende system forekommer der som ovenfor nævnt tab på ca. 25 til ca. 50% af de totale medikamentdoser.It serves to decelerate a dispensed portion of aerosol to deliver the dispersed powder at low speed, to absorb the moment of movement of the aerosol stream, 15 before the suspended powder enters the user's mouth, to complete the evaporation of the aerosol propellant, to eliminate the possibility of liquid propellant reaches the mouth, to dilute the propellant and suspended powder with air, and to provide uniform and acceptable powder losses so that uniform doses are administered. It is desirable that a major portion of a discharged or dispensed drug be consumed by the user, but it is more important that each dose be consistent and predictable in size and absorbability so that a known uniform dose is administered at each actuation or release of the trigger button. A considerable loss percentage can be accepted if it is reliably uniform. With the present system, as mentioned above, losses of approx. 25 to approx. 50% of the total drug doses.
30 Decelerationskammeret indfanger meget af det medikament, der ellers ville afsættes i brugerens mund, således at en forholdsvis lille mængde af medikamentet afsættes i munden sammenlignet med den mængde, der når frem til lungerne og er effektiv i lungerne.The deceleration chamber captures much of the drug that would otherwise be deposited in the user's mouth, such that a relatively small amount of the drug is deposited in the mouth compared to the amount reaching the lungs and is effective in the lungs.
35 Systemet er især indrettet til brugen af så danne medikamenter som triamcinolonacetonid og N,N-diethyl-4-The system is particularly adapted for the use of such drugs as triamcinolone acetonide and N, N-diethyl-4-
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-methyl-l-piperazin-carboxamidpamoat (også kaldet diethyl-carbamazinpamoat), som begge er værdifulde ved behandlingen af astma, og som man begge ønskeligt indgiver i små kendte ensartet nøjagtige doser, der primært absorberes i lunge-5 systemet, men ikke i næsen og halsen. Den fysiologiske effektivitet forøges ved muligheden for at forøge koncentrationen af indgivne medikamenter til den ønskede lokalitet sammenlignet med den koncentration, der kan opnås, når medikamenterne indgives systemisk.-methyl-1-piperazine carboxamide pamoate (also called diethyl carbamazine pamoate), both of which are valuable in the treatment of asthma, and both of which are desirably administered in small known uniformly accurate doses, which are primarily absorbed in the pulmonary system but not in nose and throat. Physiological efficacy is enhanced by the possibility of increasing the concentration of drugs administered to the desired site compared to the concentration attainable when the drugs are administered systemically.
10 Fortrinsvis er decelerations- og ekspansions kammeret indrettet til fuldstændig at indelukke og fastholde aerosolbeholderen under opbevaring, idet systemet samles i én stilling til opbevaring og transport og i en anden til brug. Idet aggregatet er forsynet med støvdække 15 og forseglingsorganer, er det i opbevarings- og transportstilling beskyttet mod forurenende støv og kan bekvemt bæres i lommen af brugeren og dog hurtigt samles med minimal risiko for forurening af indeholdet til brugs-tidspunktet .Preferably, the deceleration and expansion chamber is arranged to completely enclose and retain the aerosol container during storage, the system being assembled in one position for storage and transport and in another for use. As the unit is provided with dust cover 15 and sealing means, it is protected from contaminated dust in storage and transport and can be conveniently carried in the pocket of the user, yet quickly assembled with minimal risk of contamination of the contents at the time of use.
20 Opfindelsen vil i det følgende blive forklaret nærmere under henvisning til tegningen, på hvilken fig. 1 viser et perspektivbillede af aerosoldispenseren samlet i dosisafgivelsesstilling, fig. 2 viser delvis i snit dispenseren i op-25 bevarings- og transportstilling, fig. 3 er et forstørret snitbillede, der viser ventilen samlet med ekspansionskammerafdækningen og især en antidræntank, der skal sikre, at doseringsventilen til stadighed er overskyllet med drivmiddel og således be-30 skyttet mod helt eller delvis at løbe tør med deraf følgende uregelmæssige doseringer, fig. 4 viser det samme ventilaggregat i sammenpresset stilling efter afgivelse af en dosis, hvorved ventilstemplet er presset i bund, og 35 fig. 5 viser en anden konfiguration, ved hvilken udløserknappen til opbevaring passer ind i en aftagelig 5The invention will be explained in more detail below with reference to the drawing, in which 1 is a perspective view of the aerosol dispenser assembled in a dose delivery position; FIG. 2 is a partial sectional view of the dispenser in the storage and transport position; FIG. Figure 3 is an enlarged sectional view showing the valve assembled with the expansion chamber cover and, in particular, an anti-drain tank which is intended to ensure that the metering valve is continuously flushed with propellant and thus protected against completely or partially running out with consequent irregular dosages; 4 shows the same valve assembly in compressed position after delivery of a dose whereby the valve piston is pressed into the bottom, and FIG. 5 shows another configuration in which the storage release button fits into a removable 5
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afgivelsesdyse.dispensing nozzle.
Således som vist i tegningens fig. 1 er aerosol-dispenserens største bestanddel eller element et decellerationskammer 11, der fortrinsvis er af plast 5 såsom polyethylen. Decellerationskammeret har et cylindrisk hus eller en tønde 12, der hensigtsmæssigt kan have en længde på ca. 7 cm, en indvendig diameter på ca. 4 cm og en vægtykkelse på ca. 1,5 mm. Ved dens ene ende findes et mundstykke 13, der bekvemt har en ydre diameter på 10 ca. 2 cm og er 1,5 cm langt, hvilket er en størrelse, der bekvemt fastholdes mellem brugerens læber, idet læberne danner et i det væsentlige lufttæt lukke omkring mundstykket. Mundstykket er fastgjort til den cylindriske tønde 12 ved hjælp af overgangen 14. Hensigtsmæssigt, men 15 ikke nødvendigvis, er overgangen og den cylindriske tønde støbt i ét stykke af plast såsom lineær polyethylen. Dette giver en økonomisk fremstillingsmetode og en glat, let bearbejdelig overflade, som er let at gøre ren. En aftagelig mundstykkekapsel 15 er sammenpasset i støvtæt for-20 bindelse med mundstykket. Kapslen kan glide eijten indvendigt eller udvendigt med fingerfriktionspasning. Ved udtrykket "fingerfriktionspasning" forstås her en friktions--sammenhæng, der vil holde stykkerne sammen under normale håndteringsbetingelser, men som let kan aftages eller på-25 sættes kun med fingertryk. Mundstykkekapslens udvendige overflade kan være ru eller rouletteret således, at den er lettere at få fat i med fingrene. Mundstykkekapslens og mundstykkets kanter kan være affasede eller let afrundede i overensstemmelse med konventionel praksis, så det er 30 let at sætte kapslen på plads, og andre kanter i apparatet kan ligeledes være affasede eller afrundede. Enten mundstykket eller mundstykkekapslen kan have små ribber af størrelsesordenen 0,05 mm for at formindske friktion og lette påsætning. Ved at være forsynet med sådanne frem-35 springende dele eller punkter på friktionspåvirkede anlægsdele udnyttes den naturlige elasticitet hos piastma-As shown in FIG. 1, the largest component or element of the aerosol dispenser is a deceleration chamber 11 which is preferably of plastic 5 such as polyethylene. The deceleration chamber has a cylindrical housing or barrel 12 which may conveniently have a length of approx. 7 cm, inside diameter of approx. 4 cm and a wall thickness of approx. 1.5 mm. At its one end is a nozzle 13 which conveniently has an outer diameter of about 10 mm. 2 cm and 1.5 cm long, which is a size that is conveniently held between the user's lips, the lips forming a substantially airtight closure around the mouthpiece. The nozzle is attached to the cylindrical barrel 12 by means of the transition 14. Conveniently, but not necessarily, the transition and the cylindrical barrel are molded in one piece of plastic such as linear polyethylene. This provides an economical manufacturing method and a smooth, easily workable surface that is easy to clean. A removable nozzle capsule 15 is fitted in dustproof connection with the nozzle. The capsule can slide inside or outside with finger friction fit. The term "finger friction fit" here means a frictional bond which will hold the pieces together under normal handling conditions, but which can be easily removed or applied only with finger pressure. The outer surface of the nozzle capsule may be rough or rotated so that it is easier to grasp with the fingers. The edges of the nozzle capsule and nozzle may be beveled or slightly rounded in accordance with conventional practice, so that it is easy to put the capsule in place, and other edges of the apparatus may also be beveled or rounded. Either the nozzle or the nozzle capsule may have small ribs of the order of 0.05 mm to reduce friction and ease of application. By providing such protruding parts or points on frictionally impacted abutment parts, the natural elasticity of the
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terialet såsom polyethylen til at tilvejebringe et friktionsanlæg, der let kan bringes til ophør med fingrene, og vel at mærke uden at det er nødvendigt med dyre foranstaltninger som fremstilling og sammenpasning af stykkerne 5 med stor nøjagtighed. Lignende detaljer som ved denne samling kan benyttes andre steder i den foreliggende dispenser, idet de er konventionelle inden for plaststøbetek-nikken.the material, such as polyethylene, to provide a frictional system which can be easily terminated with the fingers and well felt without the need for expensive measures such as manufacturing and fitting the pieces 5 with great accuracy. Similar details can be used in this assembly elsewhere in the present dispenser, being conventional in the plastics molding technique.
Ved den åbne ende af den cylindriske tønde 12 10 findes en beholderopspænding 16. Beholderopspændingen er et element med flere funktioner. En holderflange 17 passer tværs over den åbne ende af den cylindriske tønde 12.At the open end of the cylindrical barrel 12 10 there is a container clamp 16. The container clamp is a multi-function element. A holder flange 17 fits across the open end of the cylindrical barrel 12.
En anbringelsesmanchet 18 ligger an ved enden af den cylindriske tønde 12. Hensigtsmæssigt, men ikke nødvendig-15 vis, passer anbringelsesmanchetten indvendigt i den cylindriske tønde 12 med en friktions-tilpasning, og anbringelsesmanchetten er lang nok til at hindre tilfældig adskillelse, men vil samtidig sikre let fjernelse af beholderopspændingen 16. Hensigtsmæssigt, men ikke nød-20 vendigvis, rager anbringelsesmanchetten 18 ud fra beholderflangen 17, således at dens elasticitet tillader fingerfriktionspasning af delene støbt med normal nøjagtighed. En beholderopspændingsmanchet 19 strækker sig indad fra opspændingsflangen eller fastholdelsesflangen 25 17 og har en sådan størrelse, at den passer omkring, fast holder og bringer en aerosolbeholder 20 i rigtig stilling. Hensigtsmæssigt, men ikke nødvendigvis, er aerosolbeholderen 20 af rustfrit stål eller aluminium, således at den kan rumme aerosoldrivmidler under højt tryk. Behol-30 derfastholdelsesmanchetten er lang nok og stor nok til at holde aerosolbeholderaggregatet i stilling inden i og aksialt i forhold til decellerationskammeret 11 under opbevarings- og transportfaserne, når dette organ er i brug, og til let at tillade aftagelse af aerosolbeholde-35 ren 20, når medikamentet skal indtages.An applicator sleeve 18 abuts the end of the cylindrical barrel 12. Conveniently, but not necessarily, the applicator sleeve fits inside the cylindrical barrel 12 with a frictional fit, and the applicator sleeve is long enough to prevent random separation, but will at the same time ensuring easy removal of the container clamp 16. Conveniently, but not necessarily, the mounting sleeve 18 protrudes from the container flange 17 so that its elasticity permits finger friction fitting of the parts molded with normal accuracy. A container clamping sleeve 19 extends inwardly from the clamping flange or retaining flange 25 and is of such size that it fits around, firmly holds and puts an aerosol canister 20 in proper position. Suitably, but not necessarily, is the stainless steel or aluminum aerosol container 20 so that it can hold aerosol propellants under high pressure. The container retaining cuff is long enough and large enough to hold the aerosol container assembly in position within and axially of the deceleration chamber 11 during the storage and transport phases when this member is in use, and to allow easy removal of the aerosol container 35 when to take the drug.
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Gennem fastholdelsesflangen løber ét eller flere lufthuller 21, der tilvejebringer indførelse af fortyndingsluft under brug. Tre lufthuller, som hver måler ca. 3 mm i diameter, har vist sig at give gode resulta-5 ter i denne henseende.One or more air holes 21 pass through the retaining flange which provides the introduction of dilution air during use. Three air holes, each measuring approx. 3 mm in diameter, has been found to give good results in this regard.
Ud fra fastholdelsesflangen 17 stikker en knapholder 22. Knapholderen er hul, men er lukket i den modsatte ende af fastholdelsesflangen og har deri en monteringsåbning 23, hvis størrelse og form er således 10 indrettet, at den fastholder en aerosoludløserknap 24, der skal beskrives mere detaljeret nedenfor. Da aerosoludløs erknappen skal befinde sig i en bestemt retning, er formen på monteringsåbningen 23 således, at den passer sammen med udløserknappen 24 og fastholder udløserknappen 15 i en bestemt rettet sammenhæng. Således som vist er udløserknappen cylindrisk med en flad side 25, der arbejder sammen med en viseråbningsflade 26, således at sprøjtestrømmen sendes aksialt gennem decellerationskammeret. Hensigtsmæssigt, men ikke nødvendigvis, er knapholderen 20 udformet med to monteringsåbninger 23 anbragt diametralt modsat, således at udløserknappen 24 kan indsættes fra den ene side og den anden åbning tjener som sådan som ekstra luftindgang. Ved den ende af knapholderen 22, der vender bort fra holderflangen 17, er en holdering 27, der 25 hensigtsmæssigt rager ca. 0,13 mm længere ud end knapholderens udvendige cylindriske overflade. En beskyttelsesmanchet 28 passer med let friktionsanlæg over og på knapholderens udvendige overflade. Da delene er lavet af plast, har de tilstrækkelig elasticitet til, at beskyt-30 telsesmanchetten 28 kan tvinges let over holderingen 27 og i stilling, men ikke så let fjernes, således at den holdes på plads i dispenserens nyttelevetid. Beskyttelsesmanchetten har knapåbninger 29, der tillader manchetten 28 at drejes, således at knapåbninger 29 passer sam-35 men med monteringsåbningen, og tillade, at knappen indsættes igennem denne, og stadig kan drejes ca. 90° for atFrom the retaining flange 17 protrudes a button holder 22. The button holder is hollow, but is closed at the opposite end of the retaining flange and therein has a mounting opening 23, the size and shape of which is arranged 10 to hold an aerosol release button 24, to be described in more detail. below. Since the aerosol release button has to be in a certain direction, the shape of the mounting aperture 23 is such that it fits with the release button 24 and holds the release button 15 in a specific directed context. As shown, the release button is cylindrical with a flat side 25, which cooperates with a pointer opening surface 26, so that the spray flow is axially passed through the deceleration chamber. Conveniently, but not necessarily, the button holder 20 is formed with two mounting openings 23 located diametrically opposite so that the release button 24 can be inserted from one side and the other opening serves as an additional air inlet. At the end of the button holder 22 facing away from the holder flange 17 is a holder 27 which conveniently protrudes approx. 0.13 mm longer than the outer cylindrical surface of the button holder. A protective sleeve 28 fits with light friction over and on the outer surface of the button holder. Since the parts are made of plastic, they have sufficient elasticity that the protective sleeve 28 can be easily forced over the retaining ring 27 and in position, but not so easily removed so that it is held in place during the useful life of the dispenser. The protective sleeve has button openings 29 which allow the sleeve 28 to be rotated so that button openings 29 fit together with the mounting opening, and allow the button to be inserted through it and still be able to rotate approx. 90 ° to
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beskytte aggregatet mod indtrængning af støv og smuds under opbevaring og transport.protect the unit from dust and dirt penetration during storage and transport.
I tegningens fig. 2 er dispenseren vist i bære-stilling, nemlig til opbevaring og transport, hvorved 5 aerosolbeholderen 20 fastholdes i beholderopspændings-manchetten 19 indvendigt i decellerationskammerets cylindriske tønde.In the drawing FIG. 2, the dispenser is shown in a carrier position, namely for storage and transport, whereby the aerosol container 20 is held in the container clamping sleeve 19 inside the cylindrical barrel of the deceleration chamber.
Aerosolbeholderen 20 er lukket med en ventilsamling 30, der indbefatter en rørring 31 til at holde 10 ventilen i stilling, og ud fra denne ventilsamling stikker udløserknappen 24.The aerosol container 20 is closed with a valve assembly 30 which includes a pipe ring 31 for holding the valve in position and from this valve assembly the release button 24 projects.
Således som vist i tegningens fig. 3, som vedrører apparatet til brugstidspunktet, aftages mundstykkekapslen 15, fjernes holderflangen 17 fra den anden ende 15 af den cylindriske tønde, aftages aerosolbeholderen 20 fra beholderopspændingsmanchetten 19, drejes beskyttelsesmanchetten 28, indtil knapåbningen 29 er i register med monteringsåbningen 23, og samles apparatet i dosisafgivelsesstilling ved, at udløserknappen 24 indsættes gen-20 nem knapåbningen 29 i en af viseråbningerne 13, således at sprøjteåbningen 32 er aksial og koncentrisk med den cylindriske tønde 12 i decellerationskammeret, og således at udtømningen fra aerosolbeholderen sker symmetrisk i henseende til decellerationskammerets opbygning.As shown in FIG. 3, which relates to the apparatus at the time of use, the nozzle cap 15 is removed, the retaining flange 17 is removed from the other end 15 of the cylindrical barrel, the aerosol container 20 is removed from the container clamping sleeve 19, the protective sleeve 28 is rotated until the button opening 29 is in register with the mounting opening 23, and dose delivery position by inserting the release button 24 through the button opening 29 in one of the display openings 13 such that the syringe opening 32 is axial and concentric with the cylindrical barrel 12 in the deceleration chamber and so that the discharge from the aerosol container takes place symmetrically with respect to the deceleration chamber.
25 Således som vist i fig. 3 vender aerosolbehol deren 20 i dosisafgivelsesstillingen opad, således at medikamentet i drivmidlet 33 ved tyngdens kraft trækkes ned mod ventilaggregatet 30.25 As shown in FIG. 3, the aerosol container 20 in the dose delivery position faces upwardly so that the drug in the propellant 33 is pulled down by gravity against the valve assembly 30.
Udløserknappen 24 har en sprøjteåbning 32, 30 der hensigtsmæssigt er indboret på tværs af knappen, og har en sprøjteåbning 34, igennem hvilken medikamentet i drivmidlet udtømmes. Denne sprøjteåbning kan enten være udformet sammenhængende med sprøjteknappen eller være lavet af en særskilt metalindsætning. Begge typer er kon-35 ventionelle konstruktioner. Sprøjteåbningen bør have enThe release button 24 has a syringe opening 32, 30 which is conveniently drilled across the button and has a syringe opening 34 through which the drug in the propellant is discharged. This syringe opening can either be formed in conjunction with the syringe button or be made of a separate metal insert. Both types are conventional designs. The syringe opening should have one
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sådan diameter, at den afgivne eller udtømte dosis dis-pergeres i findelt form som en kegle ved afgangen fra sprøjteåbningen.such a diameter that the dispensed or discharged dose is dispersed in finely divided form as a cone at the exit from the syringe opening.
En åbning på ca. 0,38 til 0,46 mm giver et 5 godt sprøjtemønster.An opening of approx. 0.38 to 0.46 mm gives a good 5 spray pattern.
Udløserknappen 24 passer fint omkring enden af en ventilstamme 35, som rager ind i ventillegemet 36.The release button 24 fits nicely around the end of a valve stem 35 which projects into the valve body 36.
I ventillegemet 36 findes et doseringskammer 37, i hvilket ventilstammen 35 er glidbart monteret. Mellem ven-10 tillegemet' og fastspændingsringen 31 findes en doseringspakning 38, der opfylder en dobbelt funktion, idet den tjener som forseglende lukke mod tab af drivmiddel, når ventilstempelmanchetten 39 presser mod doseringspakningen, og den tjener som ringlukke omkring ventilstammen 35, 15 således at en doseringsåbning 41 i ventilstammen, efterhånden som ventilstammen presses mod en ventilfjeder 40, passerer doseringspakningen og tillader doseringskammerets indhold at passere gennem doseringsåbningen 41, en aksial ventilstammeudboring, som løber gennem venti1-20 stammen, og ind i en udtømningsåbning 43 i udløserknappen 24 til sprøjteåbningen 34. Ved den indre ende af ventilstammen 45 findes påfyldningsnoter 44. Disse arbejder sammen med en påfyldningspakning 45, som holdes mod den nedre ende af doseringskammeret ved hjælp af en spænde-25 skive 46 af rustfrit stål for ventilstammen, som på sin side holdes mod bunden af doseringskammeret 37 ved hjælp af ventilfjederen 40. I drift, medens ventilstammen 35 er presset ned, passerer ventilstammen 35 gennem påfyldningspakningen 45, således at påfyldningsnoterne passerer 30 gennem påfyldningspakningen og den fulde diameter af ventilstammen 35 lukker tæt af mod påfyldningspakningen 45, således at doseringskammeret fyldes og lukkes ved den indre ende, før doseringsåbningen 41 passerer doseringspakningen 38, der tillader doseringskammerets ind-35 hold at udtømmes gennem doseringsåbningen 41, den aksiale ventilstammeudboring 42, udtømningsåbningen 43 og sprøjteåbningen 34.In the valve body 36 there is a metering chamber 37 in which the valve stem 35 is slidably mounted. Between the valve body and the clamping ring 31 is a metering gasket 38 which fulfills a dual function, serving as a seal against loss of propellant as the valve piston sleeve 39 presses against the metering gasket and serves as a ring closure around the valve stem 35, 15 so that a metering opening 41 in the valve stem, as the valve stem is pressed against a valve spring 40, passes the metering gasket and permits the metering chamber contents to pass through the metering opening 41, an axial valve stem bore running through the valve stem 20, and into an exhaust port 43 in the ejection button 24 34. At the inner end of the valve stem 45 are fill notes 44. These work together with a filling gasket 45 which is held against the lower end of the metering chamber by means of a stainless steel washer 46 for the valve stem which is in turn held against bottom of dosing chamber 37 by valve spring The eedder 40. In operation, while the valve stem 35 is depressed, the valve stem 35 passes through the filling gasket 45 such that the filling notes 30 pass through the filling gasket and the full diameter of the valve stem 35 closes tightly against the filling gasket 45 so that the metering chamber is filled and closed at the inner end, before the metering opening 41 passes the metering seal 38 allowing the contents of the metering chamber 35 to be discharged through the metering opening 41, axial valve stem bore 42, discharge opening 43, and syringe opening 34.
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Fig. 4 viser udløserknappen 24 i nedtrykt stilling med ventilen indstillet på afgivelse eller udtømning .FIG. 4 shows the release button 24 in the depressed position with the valve set to discharge or discharge.
Når trykket på udløserknappen 24 slippes, 5 skubbes ventilstammen 35 udad med ventilfjederen 40, således at doseringsåbningen 41 passerer doseringspakningen 38, der lukker afgivelsen eller udtømningen fra doseringskammeret, og senere passerer påfyldningsnoterne 44 påfyldningspakningen 45, der tillader drivmiddel in-10 deholdende medikamentet at strømme gennem påfyldningsnoterne 44 og igen fylde doseringskammeret 37.When the pressure of the release button 24 is released, the valve stem 35 is pushed outwardly with the valve spring 40 such that the metering opening 41 passes the metering gasket 38 which closes the discharge or discharge from the metering chamber, and later the filling notes 44 pass the filling gasket 45 allowing the propellant to contain flowing drug. through the filling notes 44 and again filling the metering chamber 37.
Ventillegemet 36 har en ventillegemsflange 47, der dækker enden af aerosolbeholderen 20 og er lukket tæt imod denne ved hjælp af en beholderpakning 48. Rørholde-15 ren 31 fastholder aggregatet i stilling mod enden af aerosolbeholderen 20, idet rørholderen 31 er undersænket på den rustfri stål- eller aluminium-aerosolbeholder 20.The valve body 36 has a valve body flange 47 which covers the end of the aerosol container 20 and is closed tightly against it by means of a container gasket 48. The tube holder 31 holds the assembly in position against the end of the aerosol container 20, the tube holder 31 being submerged on the stainless steel. - or aluminum aerosol container 20.
Den oven for beskrevne konstruktion for en doseringsventil er blot én type af doseringsventil. Andre 20 konventionelle typer af doseringsventiler kan dog benyttes, om ønsket.The design described above for a metering valve is just one type of metering valve. However, other 20 conventional types of metering valves can be used, if desired.
Da doseringsventiludtømningerne har en forholdsvis lille størrelse, idet f.eks. ca. 50 mikroliter pr. udløsning er en bekvem størrelse ved sådanne kommer-25 cielle apparater, og da hver enkelt udtømning har et rumfang på nogenlunde det samme som en lille vanddråbe, er det vigtigt, at doseringskammeret er fuldstændigt fyldt før hver udløsning, og at doseringskammerets indhold forhindres i at løbe tilbage til aerosolbeholderen mellem to 30 udløsninger. Dette tab af påfyldning hindres med en antidræntank 49. Antidræntanken 49 passer ind i en flangemanchet 50 på ventillegemsflangen 47, hvilken flangemanchet 50 har en indre cylindrisk overflade, imod hvilken antidræntanken 49 lægger an med stram friktionstilpasning.Since the metering valve discharges have a relatively small size, e.g. ca. 50 microliters per Discharge is a convenient size for such commercial appliances, and since each discharge has a volume of roughly the same as a small drop of water, it is important that the metering chamber is completely filled before each release and that the contents of the metering chamber are prevented from run back to the aerosol container between two 30 releases. This loss of filling is prevented by an anti-drain tank 49. The anti-drain tank 49 fits into a flange sleeve 50 of the valve body flange 47, which flange sleeve 50 has an inner cylindrical surface against which the anti-drain tank 49 abuts with tight friction fitting.
35 I randen af antidræntanken 49 og mellem antidræntanken og flangemanchetten 50 findes en påfyldningsgennemgang 51, Ο η DK 152967Β der tjener til genfyldning af antidræntanken fra hovedmassen af medikament i drivmiddel, der befinder sig i resten af aerosolbeholderen.35 At the rim of the anti-drain tank 49 and between the anti-drain tank and flange sleeve 50 there is a filling passageway 51, η η DK 152967Β, which serves to refill the anti-drain tank from the main body of propellant drug present in the remainder of the aerosol container.
For at beskytte antidræntanken mod at slippe 5 eller falde af ved et tilfældigt uheld, f.eks. ved at aerosolbeholderen falder på gulvet under brug, er dræntanken efter anbringelse i stilling ultralydsvejset under anvendelse af et ultralydlukke, i hvilket ultralydenergien sendes gennem flangemanchetten til antidræntanken. Ved 10 påsvejsning sendes energi igennem samlingen, idet der er en diskontinuitet mellem antidræntanken og flangemanchetten, således at energien reflekteres og brydes, hvilket får ultralydenergien til at sive ud og vise sig som varme, der smelter materialet og derved forsegler antidræntanken 15 til flangemanchetten. Ved en sådan ultralydforsegling bliver aggregatet økonomisk forsvarligt at fremstille og effektivt i brug. Når antidræntanken er forseglet således, bliver den på plads under en hvilken som helst brug eller misbrug, som der ikke ligefrem ødelægger selve aerosol-20 beholderen.To protect the anti-drain tank from dropping 5 or falling off accidentally, e.g. in that the aerosol container falls to the floor during use, the drain tank after being placed in position is ultrasonically welded using an ultrasonic closure in which the ultrasonic energy is sent through the flange sleeve to the anti-drain tank. At welding, energy is transmitted through the assembly, there being a discontinuity between the anti-drain tank and the flange sleeve so that the energy is reflected and refracted, causing the ultrasonic energy to seep out and appear as heat, which melts the material, thereby sealing the anti-drain tank 15 to the flange sleeve. With such an ultrasonic seal, the unit becomes economically sound to manufacture and efficiently used. When the anti-drain tank is sealed thus, it remains in place during any use or abuse which does not exactly destroy the aerosol container itself.
Når udløserknappen presses ned, medens aerosolbeholderen befinder sig i afgivelsesstilling, udtømmes doseringskammerets indhold på grund af drivmidlets natur med deraf følgende afgivelse af den ønskede afmålte por-25 tion, og når udløserknappen slippes, indsuges en ny portion fra antidræntanken i doseringskammeret, og antidræntanken fyldes igen gennem adgangsåbningen 51. Antidræntanken forbliver fyldt med drivmidlet indeholdende medikamentet uafhængigt af aerosolbeholderens orientering.When the shutter button is depressed while the aerosol container is in the dispensing position, the contents of the metering chamber are discharged due to the nature of the propellant with consequent release of the desired metered portion, and when the shutter release button is released, a new portion of the anti-drain tank is sucked into the metering chamber and again through the access opening 51. The anti-drain tank remains filled with the propellant containing the drug, regardless of the orientation of the aerosol container.
30 Således afgives en forudsigelig, ensartet, nøjagtig dosis ved hver udløsning af udløserknappen.Thus, a predictable, uniform, accurate dose is delivered at each release of the trigger button.
Idet den med notudboringer forsynede ende af ventilstangen holdes neddyppet i flydende drivmiddel hele tiden, opretholdes homogeniteten af det faste fin-35 delte medikament i drivmidlet mere ensartet, og der afgives mere konsekvent ensartede doser. Anvendelsen af enAs the end bore end of the valve rod is kept immersed in liquid propellant all the time, the homogeneity of the solid finely divided drug in the propellant is maintained more uniformly and more consistently uniform doses are delivered. The use of one
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plast-antidræntank synes at hjælpe til ved at neutralisere elektriske ladninger, der ellers ville ophobes i systemet.Plastic anti-drain tank seems to help by neutralizing electrical charges that would otherwise accumulate in the system.
Med en rustfri stålaerosolbeholder 20 holdes 5 omkredsen af drivmiddelportionen effektivt på et enkelt potential; men drivmidlet kan optræde som et dielektri-kum, således at de individuelle medikamentpartikler oplades, hvilket påvirker deres dispergering og udtømningshastighed. Med antidræntanken neutraliseres den rustfrie 10 stålbeholders virkning i det mindste delvis, således at statiske virkninger formindskes eller minimeres og tillader mere ensartede udtømningsegenskaber.With a stainless steel aerosol container 20, the circumference of the propellant portion is effectively maintained at a single potential; but the propellant may act as a dielectric so that the individual drug particles are charged, which affects their dispersion and discharge rate. With the anti-drain tank, the effect of the stainless steel container is at least partially neutralized so that static effects are diminished or minimized and allow for more uniform depletion properties.
I fraværelse af antidræntanken viser de første 25% afgivne doser sig at have højere koncentration end de 15 sidste 25%, således at brugeren modtager mere medikament end forudset fra en ny dispenser og mindre end forudset fra en næsten tom dispenser. Med den foreliggende antidræn-tank minimeres variationen i ladninger, således at brugeren opnår en mere pålidelig ensartet dosering af medika-20 mentet.In the absence of the anti-drain tank, the first 25% of doses delivered appear to have a higher concentration than the last 15%, so that the user receives more drug than anticipated from a new dispenser and less than predicted from an almost empty dispenser. With the present anti-drain tank, the variation in charges is minimized so that the user achieves a more reliable uniform dosage of the drug.
Det er vanskeligt at måle virkningen af elektriske ladningerinden i aerosolbeholderen og i decellera-tionskammeret; men uafhængigt af den teoretiske og videnskabelige baggrund til forklaring af ladningens ens-25 artethed har det dog vist sig, at med den her omhandlede antidræntank afgives mere ensartede doser, og med de-cellerationskammeret, i hvilket mundstykket har mindre end halvdelen af den cylindriske tøndes tværsnitsareal, og den cylindriske tøndes længde er mindre end to gange 30 dens diameter, dispergeres de individuelle doser af medikament i drivmiddel i decellerationskammeret og taber her strålehastigheden, som meddeles det ved hjælp af drivmiddelsprøjtningen. Hvis nogen partikler stadig beholder hastighed, rammer de enten decellerationskammerets væg 35 eller holdes tilbage derpå, eller de stødes bort fra væggene, således at der dannes en dispergeret pulvermængde,It is difficult to measure the effect of the electric charge in the aerosol container and in the deceleration chamber; however, regardless of the theoretical and scientific background for explaining the uniformity of the charge, it has been found, however, that with the antidrain tank at issue, more uniform doses are dispensed, and with the decellation chamber, in which the nozzle has less than half the cylindrical barrel cross-sectional area, and the length of the cylindrical barrel is less than twice its diameter, the individual doses of propellant drug are dispersed in the deceleration chamber and here lose the jet velocity communicated by the propellant spray. If any particles still retain velocity, they either hit or retain the wall of the deceleration chamber, or be pushed away from the walls to form a dispersed amount of powder.
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der vil blandes op med ekstra fortyndingsluft og inhaleres, efterhånden som brugeren inhalerer det findelte medikament gennem mundstykket. En stor del af medikamentet, som ellers ville afsættes i brugerens mund og føl-5 gelig absorberes systemisk, afsættes på decellerations-kammerets vægge.which will be mixed with extra dilution air and inhaled as the user inhales the comminuted drug through the mouthpiece. A large portion of the drug, which would otherwise be deposited in the mouth of the user and subsequently absorbed systemically, is deposited on the walls of the deceleration chamber.
Selv om medikamentet kan være ret kostbart, er doseringerne så små, at et tab på ca. 25 til 50% i de-cellerationskammeret alligevel er i høj grad acceptabelt 10 sammenlignet med fordelene ved overensstemmende og ensartet forudsigelig dosering, der kan indgives til patienten.Although the drug can be quite expensive, the dosages are so small that a loss of approx. Nevertheless, 25 to 50% in the de-cellation chamber is highly acceptable 10 compared to the advantages of consistent and uniformly predictable dosage which may be administered to the patient.
Ved mange droger eller medikamenter er det meget vigtigt, at nøjagtigt den foreskrevne eller ønskede mængde indgives til brugeren. Ensartethed er vigtig, så-15 ledes at lægen, der foretager indgivelsen, ved, hvilke justeringer man behøver at foretage i doseringsniveauet afhængigt af brugerens respons.For many drugs or medications, it is very important that exactly the prescribed or desired amount is administered to the user. Uniformity is important so that the physician making the administration knows what adjustments need to be made in the dosage level depending on the user's response.
I fig. 5 er vist en modifikation af aerosol--dispensersystemet, i hvilket beholderopspændingsmanchet-2o ten af den viste type benyttes sammen med en afgivelsesdyse 52, der passer i holderflangen 53 sammen med aerosolbeholderens bundstykke,, der går snævert ind i påføringsdysen. Glidbart monteret og tilpasset i den anden ende af påføringsdysen findes en knapholderslæde 54, som 25 kan presses indad til forsegling eller trækkes udad til fastholdelse af udløserknappen i driftsstilling.In FIG. 5, there is shown a modification of the aerosol dispenser system in which the container clamping sleeve 2 of the type shown is used in conjunction with a dispensing nozzle 52 which fits in the holder flange 53 together with the bottom piece of the aerosol dispenser which narrows into the application nozzle. Slidably mounted and fitted at the other end of the applicator nozzle there is a button holder slide 54 which can be pressed inwardly for sealing or pulled outward to hold the release button in the operating position.
Andre konfigurationer kan anvendes, forudsat decellerationskammeret er stort nok til at opbremse den afgivne aerosolportion og tillade inhalationshastighe-30 den fra brugerens inhalation at være den eneste faktor til bestemmelse af afgivelseshastigheden til brugstidspunktet. Med en doseringsfælde, der rummer ca. 50 mikro-liter materiale, opsuges udtømningsenergien fuldstændig i decellerationskammeret, og der dannes en fin aerosol, 35 næsten en røg af medikamentet, der skal indgives, og denne fine aerosol inhaleres i lungerne.Other configurations may be used, provided the deceleration chamber is large enough to slow the delivered aerosol portion and allow the inhalation rate from the user's inhalation to be the only factor determining the delivery rate to the time of use. With a dosing trap that holds approx. 50 microliters of material, the depletion energy is completely absorbed into the deceleration chamber and a fine aerosol is formed, almost a smoke of the drug to be administered and this fine aerosol inhaled into the lungs.
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14 -14 -
En røg defineres normalt som en suspension af fine faste partikler i en gas, således som den kan frembringes ved ild, idet partikelstørrelsen ligger i det kolloide område. Her ligger partikelstørrelsen i overlap-5 ningen mellem det kolloide område og den nedre ende af området for partikler lidt større end et sandt kolloid.A smoke is usually defined as a suspension of fine solid particles in a gas as it can be produced by fire, the particle size being in the colloidal region. Here, the particle size lies in the overlap between the colloidal region and the lower end of the particle region slightly larger than a true colloid.
De forskellige definitioner på partikelstørrelsesområder overlapper dog hinanden i en vis grad.However, the various definitions of particle size ranges overlap to some extent.
Til den foreliggende opfindelses formål defi-10 neres partikelstørrelsen som liggende fra 0,5 pm til 10 pm, hvilket har vist sig at give gode resultater. Partikler med en størrelse over ca. 10 pm er for tilbøjelige til at afsættes i munden eller halsen på brugeren, og de foretrækkes derfor ikke til inhalationsterapi. Nogle få par-15 tikler i dette størrelsesinterval er sædvanligvis ikke skadeligt, men de bidrager i uforholdsmæssig høj grad til den systemiske absorption fremfor at absorberes gennem lungerne.For the purposes of the present invention, the particle size is defined as ranging from 0.5 µm to 10 µm, which has been found to give good results. Particles with a size over approx. 10 µm are too likely to be deposited in the mouth or throat of the user and are therefore not preferred for inhalation therapy. A few par-15 ticks in this size range are usually not harmful, but they contribute disproportionately to systemic absorption rather than being absorbed through the lungs.
Når det her omhandlede apparat først er taget 20 i brug, bør kammeret lejlighedsvis vaskes, fordi en del af medikamentet afsættes på decellerationskammerets vægge.Once the apparatus in question is first used, the chamber should occasionally be washed because part of the drug is deposited on the walls of the deceleration chamber.
Til sikring af fornøden eller passende disper-gering af det pulveriserede medikament i drivmidlet foretrækkes et drivmiddel med forholdsvis højt tryk. Dichlor-25 difluormethan ("Freon®12"), der ved stuetemperatur har et absolut tryk på ca. 5,6 atmosfære, giver gode resulta ter. En rustfri stål- eller aluminiumbeholder foretrækkes til sådanne tryk for at undgå ødelæggelse ved brud. Glasbeholdere eller plastbeholdere eller en plastovertrukket 30 0g beskyttet glasbeholder kan anvendes; men disse benyttes dog mere hensigtsmæssigt ved lavere tryk, nemlig af størrelsesordenen 2,1 til 3,4 ato.To ensure the necessary or appropriate dispersion of the powdered drug in the propellant, a relatively high pressure propellant is preferred. Dichloro-difluoromethane ("Freon®12") which at room temperature has an absolute pressure of approx. 5.6 atmosphere, gives good results. A stainless steel or aluminum container is preferred for such pressures to avoid breakage. Glass containers or plastic containers or a plastic coated 30g protected glass container may be used; however, these are more conveniently used at lower pressures, of the order of 2.1 to 3.4 ato.
En plastventilstamme foretrækkes fremfor metal, da plastventilstammen i mindre grad er udsat for at binde 35 eller hænge fast på grund af pulver, som pakkes tæt sammen omkring den. En lille mængde alkohol på ca. 1% til 10%A plastic valve stem is preferred over metal, since the plastic valve stem is less likely to bind 35 or stick because of powder which is tightly packed around it. A small amount of alcohol of approx. 1% to 10%
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fungerer som smøremiddel/ der skal holde ventilvirkningen pålidelig. Nogle medikamenter i drivmiddelsystemer fungerer dog pålideligt uden smøremiddel.acts as a lubricant / to keep the valve action reliable. However, some drugs in propellant systems work reliably without lubricant.
Det er klart, at beholderens og doseringskam-5 merets størrelse kan variere inden for vide grænser, hvilket afhænger af den dosis, som ønskes udløst, og af antallet af doser, som ønskes indgivet til en patient.It is to be understood that the size of the container and dosing chamber may vary within wide limits, depending on the dose desired to be triggered and on the number of doses desired to be administered to a patient.
I de følgende eksempler belyses nærmere anvendelsen af nogle specielle lægemidler i forbindelse med 10 en inhalator ifølge opfindelsen.In the following examples, the use of some special drugs in connection with an inhaler according to the invention will be further elucidated.
' Eksempel 1 N,N-diethyl-4-methyl-l~piperazincarboxamidpa-moat sendes gennem en væskedrevet pulveriseringsmølle og 15 findeles til en partikelstørrelse på 0,5 til 10 ;um, idet 90 vægtprocent af partiklerne ligger i størrelsesintervallet fra 1 til 5 yum, 300 mg deraf i tør form indføres i en 19 ml rustfri stålbeholder indrettet til påmontering af en aerosoldoseringssprøjtedyse, og hertil sættes 20 0,75 g vandfri ethanol. Nedkølet (-40°C) dichlordifluorme- than tilsættes fra en tryktank til den åbne beholder, hvilket ved fordampningsafkøling hurtigt nedkøler beholderen og dens indhold, idet der tilsættes tilstrækkeligt af drivmidlet til, at beholderen herefter rummer 15 g 25 dichlordifluormethan, hvorefter beholderen lukkes med en doseringsventil, som fastgøres forseglet til beholderen.Example 1 N, N-Diethyl-4-methyl-1-piperazine carboxamide powder is passed through a liquid-powered pulverization mill and comminuted to a particle size of 0.5 to 10 µm, with 90% by weight of the particles ranging in size from 1 to 5 yum, 300 mg thereof in dry form is introduced into a 19 ml stainless steel container arranged for mounting an aerosol dosing spray nozzle, to which is added 20 0.75 g of anhydrous ethanol. Cooled (-40 ° C) dichlorodifluoromethane is added from a pressure tank to the open container, which upon evaporation cooling rapidly cools the container and its contents, adding sufficiently of the propellant for the container to then contain 15 g of 25 dichlorodifluoromethane, after which the container is closed. a metering valve which is sealed to the container.
Der benyttes en doseringsventil, som afgiver 50 mikroliter indhold pr. udløsning, hvilket giver 1,3 mg N,N-diethyl-4-methyl-l-piperazincarboxamidpamoat pr. ud-30 løsning sammen med 65 mg dichlordifluormethan og 3,25 mg ethanol, der udtømmes eller afgives samtidigt. Disse er flygtige og-blandes med tilstrækkelig luft til, at de får minimal eller ingen fysiologisk aktivitet.A metering valve is used which delivers 50 microliters of content per solution yielding 1.3 mg of N, N-diethyl-4-methyl-1-piperazine carboxamide pamoate per ml. solution, together with 65 mg of dichlorodifluoromethane and 3.25 mg of ethanol, which are discharged or released simultaneously. These are volatile and mixed with sufficient air for minimal or no physiological activity.
Afhængigt af et asmatisk anfalds grad af al-35 vorlighed bringes lindring med én eller flere inhalerede udløste doser. Inhalationsindgivelsen tilvejebringer enDepending on the severity of an asthmatic seizure, relief is achieved with one or more inhaled triggered doses. The inhalation administration provides one
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16 DK 152967 B16 DK 152967 B
hurtig og effektiv metode til indgivelse eller indtagelse, som er hurtigere effektiv end systemisk indgivelse.rapid and effective method of administration or ingestion, which is faster than systemic administration.
N,N-diethy1-4-methyl-1-pipera z incarboxamid-pamoat er mere effektivt til profylaktisk eller langvarig 5 behandling end til omgående lindring. Andre medikamenter foretrækkes til meget hurtig lindring under et asmatisk anfald. Det her omhandlede N,N-diethyl-4-methyl-l-pipera-zincarboxamidpamoat i doser indeholdende ca. 0,5 til 30 mg, beregnet som diethylcarbamazin, indgivet tre gange dagligt, 10 idet dosisniveauet indrettes efter patienten og den fornødne terapiintensitet, giver langvarig kontrol med mange asmatiske tilfælde.N, N-diethyl-4-methyl-1-pipera z incarboxamide pamoate is more effective for prophylactic or long-term treatment than for immediate relief. Other medications are preferred for very rapid relief during an asthmatic seizure. The present N, N-diethyl-4-methyl-1-piperazinecarboxamide pamoate in doses containing ca. 0.5 to 30 mg, calculated as diethylcarbamazine, administered three times daily, with the dose level adjusted to the patient and the required intensity of therapy, provides long-term control of many asthmatic cases.
Da diethylcarbamazinpamoat indgives direkte i lungerne, kræves en mindre dosis, beregnet som diethyl-15 carbamazin, end normalt til effektiv lindring, end hvis samme dosis indgives systemisk dvs. oralt, hvor kredsløbssystemet udnyttes til at føre medikamentet til lungerne.Since diethylcarbamazine pamoate is administered directly into the lungs, a smaller dose, calculated as diethyl-carbamazine, is required than usual for effective relief than if the same dose is administered systemically ie. orally, where the circulatory system is utilized to carry the drug to the lungs.
' Eksempel 2 20 TriamcinoTonacetonidExample 2 TriamcinoTonacetonide
Triamcinolonacetonid findeles i en væskedrevet mølle, indtil 90 vægtprocent har en partikelstørrelse i området fra 1 til 5 yum.Triamcinolone acetonide is comminuted in a liquid-powered mill until 90% by weight has a particle size ranging from 1 to 5 µm.
I en 19 ml rustfri stålbeholder påfyldes 30 mg 25 af det således findelte triamcinolonacetonid, 0,244 ml vandfri ethanol og 19,5 g koldt påfyldt dichlordifluorme-than ved -40QC, idet afdampning tjener til afkøling af beholderen med indhold, og således at overskud tilsættes til kompensation af fordampning. Den fyldte beholder luk-30 kes med en doseringsventil som oven for beskrevet og forsegles. Dispersion i drivmidlet forbedres, når de fyldte beholdere nedsænkes i et ultralydbad, der overfører energi fra transduceren til aerosolbeholdernes indhold.In a 19 ml stainless steel vessel, 30 mg of the triamcinolone acetonide thus divided, 0.244 ml of anhydrous ethanol and 19.5 g of cold-filled dichlorodifluoromethane are charged at -40 ° C, evaporation serves to cool the container with contents and thus excess is added to the evaporation compensation. The filled container is closed with a metering valve as described above and sealed. Dispersion in the propellant is improved when the filled containers are immersed in an ultrasonic bath which transfers energy from the transducer to the contents of the aerosol containers.
Der opnås normalt gode resultater ved rystning 35 til dispergering af triamcinolonacetonidet i systemet; men ultralyddispergering er en forfinet teknik, der skalGenerally good results are obtained by shaking 35 to disperse the triamcinolone acetonide into the system; but ultrasonic dispersion is a refined technique that must
17 DK 15296 7 B17 DK 15296 7 B
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sikre endnu mere ensartet dispersion i findelt form.ensuring even more uniform dispersion in finely divided form.
Komponenterne kan blandes, behandles ultrasonisk og trykpåfyldes. Trykpåfyldning er mere indviklet til drift i lille målestok, men foretrækkes ofte ved 5 fremstilling af beholderne i stor målestok og sparer tab af drivmiddel. Det er dog nødvendigt at konstruere ventilen specifikt til sådan trykpåfyldning.The components can be mixed, treated ultrasonically and pressurized. Pressure filling is more complicated for small-scale operation, but is often preferred in large-scale production of the containers and saves loss of propellant. However, it is necessary to design the valve specifically for such pressure filling.
Ved hver udløsning af ventilknappen afgives ca. 0,1 mg triamcinolonacetonid. Fem udløsninger fire 10 gange om dagen giver en total dosis på ca. 2 mg triamcinolonacetonid. Da en del heraf holdes tilbage i decelle-rationskammeret, og kun noget inhaleres, indgives en lille smule mere end 1 mg til en patient i et typisk tilfælde.At each release of the valve button approx. 0.1 mg triamcinolone acetonide. Five triggers four 10 times a day give a total dose of about 2 mg triamcinolone acetonide. Since part of it is retained in the decellation chamber and only slightly inhaled, a little more than 1 mg is administered to a patient in a typical case.
En systemisk dosis for en sådan patient vil være ca. 8 mg 15 til opnåelse af samme virkning. Det lavere niveau og aflevering på det foretrukne sted er således en stor fordel.A systemic dose for such a patient will be approx. 8 mg 15 to achieve the same effect. Thus, the lower level and delivery at the preferred location is a major advantage.
Patienten bør instrueres om at udløse knappen til frigivelse af medikamentet i decellerationskammeret og at inhalere således, at kun den indåndede luft meddeler 20 hastighed til de partikler, der absorberes. Patienten bør holde den indåndede dosis i nogle sekunder for at tillade absorption på lungeoverfladerne, før udånding sker. En mindre mængde af medikamentet udåndes dog.The patient should be instructed to release the drug release button in the deceleration chamber and to inhale so that only the inhaled air gives 20 velocity to the particles being absorbed. The patient should hold the inhaled dose for a few seconds to allow absorption on the lung surfaces before exhaling. However, a smaller amount of the drug is exhaled.
Det er klart, at selv om drivmidlet i de fore-25 gående eksempler er dichlordifluormethan, kan man dog også bruge andre drivmidler, specielt chlorfluoralkaner og deres blandinger.It will be understood that, although the propellant in the foregoing examples is dichlorodifluoromethane, other propellants, especially chlorofluoroalkanes and their mixtures, may also be used.
' Eksempel· 3 30 Der fremstilles en suspension afEXAMPLE 3 A suspension of
Triamcinolonacetonid, findelt til 0,5-5 /am 400 mgTriamcinolone acetonide, comminuted to 0.5-5 µm 400 mg
Dichlordifluormethan 100 mlDichlorodifluoromethane 100 ml
Sorbitantrioleat 6,9 mg 35 Triamcinolonacetonidet og sorbitantrioleatet anbringes i et bæger, og dichlordifluormethanen tilsættesSorbitan trioleate 6.9 mg 35 The triamcinolone acetonide and sorbitan trioleate are placed in a beaker and the dichlorodifluoromethane is added.
18 DK 15296 7 B18 DK 15296 7 B
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ved -4Q°C. Der dannes en suspension. Blandingen ultralydbehandles, dvs. behandles med en "Sonifier" fremstillet af Branson Sonic Power Company, Danbury, Connecticut model LS-75 med en strømtilførsel på 9 ampere i 2 minut-5 ter. Der tilsættes mere kold dichlordifluormethan efter behov for at holde rumfanget på 100 ml. Blandingen dis-pergeres ensartet og har forøget stabilitet hidrørende fra ultralydbehandlingen.at -4 ° C. A suspension is formed. The mixture is ultrasonically treated, ie. treated with a "Sonifier" manufactured by Branson Sonic Power Company, Danbury, Connecticut model LS-75 with a 9 amp power supply for 2 minutes-5 hours. More cold dichlorodifluoromethane is added as needed to keep the volume of 100 ml. The mixture is uniformly dispersed and has increased stability resulting from the ultrasound treatment.
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Rustfri stålbeholdere på 19 cm fyldes med 10 15 ml af den kolde blanding, ventiler som beskrevet ovenfor påmonteres og forsegles tætlukkende til beholderne.Stainless steel containers of 19 cm are filled with 10 15 ml of the cold mixture, valves as described above are fitted and sealed tightly to the containers.
Ved opvarmning efter opbevaring forbliver triamcinolonacetonidet dispergeret, og efter blot en let skødesløs rystning afgives ensartede doser findelt 15 triamcinolanacetonid.Upon heating after storage, the triamcinolone acetonide remains dispersed, and after just a slight careless shaking, uniform doses of triamcinolanacetonide are dispensed.
Der opnås gode resultater ved asmatikeres inhalation af præparatet afleveret på denne måde.Good results are obtained by asthmatics inhalation of the preparation delivered in this way.
Eksempel 4 20 Fremgangsmåden i eksempel 3 gentages, idet der dog benyttes 1,24 ml vandfri ethanol i stedet for sorbitantrioleat. Suspensionen er stabil efter påfyldning og opbevaring. Rystning før brug anbefales til ensartet dispergering.Example 4 The procedure of Example 3 is repeated, however, using 1.24 ml of anhydrous ethanol instead of sorbitan trioleate. The suspension is stable after filling and storage. Shaking before use is recommended for uniform dispersion.
25 Dispenseren giver forholdsvis ensartede doser fra den første udløsning, og lige til den er tom. Fem udløsninger fire gange om dagen til afgivelse af en totalmængde på ca. 2 mg triamcinolonacetonid pr. patient anbefales ved behandlingens begyndelse, idet doseringen dog 30 tilpasses på grundlag af kliniske resultater med hver særlig patient.The dispenser provides relatively uniform doses from the first release and right up until it is empty. Five triggers four times a day to deliver a total amount of approx. 2 mg triamcinolone acetonide per patient is recommended at the start of treatment, however, the dosage is adjusted 30 based on clinical results with each particular patient.
3535
Claims (2)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US37417673 | 1973-06-27 | ||
| US00374176A US3809294A (en) | 1973-06-27 | 1973-06-27 | Dispensing lung contacting powdered medicaments |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK343874A DK343874A (en) | 1975-02-17 |
| DK152967B true DK152967B (en) | 1988-06-06 |
| DK152967C DK152967C (en) | 1988-10-24 |
Family
ID=23475640
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK343874A DK152967C (en) | 1973-06-27 | 1974-06-26 | INHALATOR FOR DELIVERING SIMPLE POWDER DOSES |
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|---|---|
| US (1) | US3809294A (en) |
| JP (1) | JPS6010737B2 (en) |
| AR (1) | AR198562A1 (en) |
| AT (1) | AT342211B (en) |
| BE (1) | BE813512A (en) |
| CA (1) | CA1043208A (en) |
| CH (2) | CH577832A5 (en) |
| CS (1) | CS182257B2 (en) |
| DD (1) | DD125188A5 (en) |
| DE (1) | DE2415360C2 (en) |
| DK (1) | DK152967C (en) |
| ES (1) | ES427755A1 (en) |
| FR (1) | FR2234905B1 (en) |
| GB (1) | GB1471917A (en) |
| IE (1) | IE40616B1 (en) |
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| IT (1) | IT1003994B (en) |
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| PH (1) | PH11643A (en) |
| PL (1) | PL89980B1 (en) |
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| SU (1) | SU537614A3 (en) |
| YU (1) | YU36435B (en) |
| ZA (1) | ZA741633B (en) |
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| DE3348370C2 (en) * | 1982-10-08 | 2001-10-11 | Glaxo Group Ltd | Hand-held inhaler for powder or liq. medical inhalants |
| IT1217890B (en) * | 1988-06-22 | 1990-03-30 | Chiesi Farma Spa | DOSED AEROSOL INHALATION DEVICE |
| US5169639A (en) * | 1988-09-19 | 1992-12-08 | Edward Mendell Co., Inc. | Controlled release verapamil tablets |
| US5040527A (en) * | 1990-12-18 | 1991-08-20 | Healthscan Products Inc. | Metered dose inhalation unit with slide means |
| US5186164A (en) * | 1991-03-15 | 1993-02-16 | Puthalath Raghuprasad | Mist inhaler |
| US5993805A (en) * | 1991-04-10 | 1999-11-30 | Quadrant Healthcare (Uk) Limited | Spray-dried microparticles and their use as therapeutic vehicles |
| JP3026841B2 (en) | 1991-12-12 | 2000-03-27 | グラクソ、グループ、リミテッド | Medicine |
| IL104068A (en) | 1991-12-12 | 1998-10-30 | Glaxo Group Ltd | Surfactant-free pharmaceutical aerosol formulation comprising 1,1,1,2-tetrafluoroethane or 1,1,1,2,3,3,3-heptafluoro-n- propane as propellant |
| US5916540A (en) | 1994-10-24 | 1999-06-29 | Glaxo Group Limited | Aerosol formulations containing P134A and/or P227 and particulate medicament |
| DK0616525T3 (en) * | 1991-12-12 | 1996-01-08 | Glaxo Group Ltd | medications |
| US5658549A (en) * | 1991-12-12 | 1997-08-19 | Glaxo Group Limited | Aerosol formulations containing propellant 134a and fluticasone propionate |
| US5674471A (en) * | 1991-12-12 | 1997-10-07 | Glaxo Group Limited | Aerosol formulations containing P134a and salbutamol |
| US5744123A (en) * | 1991-12-12 | 1998-04-28 | Glaxo Group Limited | Aerosol formulations containing P134a and particulate medicaments |
| US5736124A (en) * | 1991-12-12 | 1998-04-07 | Glaxo Group Limited | Aerosol formulations containing P134a and particulate medicament |
| US5653962A (en) * | 1991-12-12 | 1997-08-05 | Glaxo Group Limited | Aerosol formulations containing P134a and particulate medicaments |
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| DE69232034T2 (en) | 1991-12-18 | 2002-06-06 | Minnesota Mining & Mfg | Aerosol compositions for drug suspensions |
| GB9322014D0 (en) * | 1993-10-26 | 1993-12-15 | Co Ordinated Drug Dev | Improvements in and relating to carrier particles for use in dry powder inhalers |
| US5839429A (en) * | 1994-03-25 | 1998-11-24 | Astra Aktiebolag | Method and apparatus in connection with an inhaler |
| US5598836A (en) * | 1995-05-26 | 1997-02-04 | Healthscan Products, Inc. | Metered dose inhalation unit with slide means |
| US5976573A (en) * | 1996-07-03 | 1999-11-02 | Rorer Pharmaceutical Products Inc. | Aqueous-based pharmaceutical composition |
| DE19740617A1 (en) * | 1997-09-16 | 1999-03-18 | Palas Gmbh | Method and device for producing a solid aerosol |
| US6293279B1 (en) | 1997-09-26 | 2001-09-25 | Trudell Medical International | Aerosol medication delivery apparatus and system |
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- 1974-06-26 DK DK343874A patent/DK152967C/en not_active IP Right Cessation
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