NO306937B1 - filling device - Google Patents
filling device Download PDFInfo
- Publication number
- NO306937B1 NO306937B1 NO915073A NO915073A NO306937B1 NO 306937 B1 NO306937 B1 NO 306937B1 NO 915073 A NO915073 A NO 915073A NO 915073 A NO915073 A NO 915073A NO 306937 B1 NO306937 B1 NO 306937B1
- Authority
- NO
- Norway
- Prior art keywords
- cavity
- opening
- filled
- gas
- filling
- Prior art date
Links
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Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65B—MACHINES, APPARATUS OR DEVICES FOR, OR METHODS OF, PACKAGING ARTICLES OR MATERIALS; UNPACKING
- B65B1/00—Packaging fluent solid material, e.g. powders, granular or loose fibrous material, loose masses of small articles, in individual containers or receptacles, e.g. bags, sacks, boxes, cartons, cans, or jars
- B65B1/04—Methods of, or means for, filling the material into the containers or receptacles
- B65B1/16—Methods of, or means for, filling the material into the containers or receptacles by pneumatic means, e.g. by suction
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65B—MACHINES, APPARATUS OR DEVICES FOR, OR METHODS OF, PACKAGING ARTICLES OR MATERIALS; UNPACKING
- B65B1/00—Packaging fluent solid material, e.g. powders, granular or loose fibrous material, loose masses of small articles, in individual containers or receptacles, e.g. bags, sacks, boxes, cartons, cans, or jars
- B65B1/30—Devices or methods for controlling or determining the quantity or quality or the material fed or filled
Landscapes
- Engineering & Computer Science (AREA)
- Mechanical Engineering (AREA)
- Quality & Reliability (AREA)
- Medicinal Preparation (AREA)
- Basic Packing Technique (AREA)
- Nozzles (AREA)
- Manufacturing Of Electric Cables (AREA)
- Seal Device For Vehicle (AREA)
- Formation And Processing Of Food Products (AREA)
- Crystals, And After-Treatments Of Crystals (AREA)
- Infusion, Injection, And Reservoir Apparatuses (AREA)
Description
Foreliggende oppfinnelse vedrører en fylleanordning, særlig en anordning for ifylling av et findelt pulvermateriale i et langt og smalt hulrom med en relativt liten åpning. Som eksempler på kjent teknikk på området kan nevnes DE-A-1 561 952 og US 4 872 493. The present invention relates to a filling device, in particular a device for filling a finely divided powder material into a long and narrow cavity with a relatively small opening. DE-A-1 561 952 and US 4 872 493 can be mentioned as examples of prior art in the area.
Det er ønskelig å kunne utdele et farmakologisk aktivt materiale i findelt pulverform til en pasient. Astma- og andre medisiner er eksempelvis blitt tildelt ved bruk av dispenseranordninger for inhalering. En vanskelighet i forbindelse med tildeling av finpulvermaterialer er, at det ofte er nødvendig å foreta nøyaktig og gjentatt fylling av lange og trange hulrom i dispenseranordningen med en enhetsdose av materialet. It is desirable to be able to dispense a pharmacologically active material in finely divided powder form to a patient. Asthma and other medicines have, for example, been allocated using dispenser devices for inhalation. A difficulty in connection with the allocation of fine powder materials is that it is often necessary to accurately and repeatedly fill long and narrow cavities in the dispenser device with a unit dose of the material.
I dette øyemed er det nylig tilveiebragt en anordning og en fremgangsmåte for innføring av et finpulverisert, fast og antibiotisk, terapeutisk middel i rothinnelommen på en pasient som lider av tannrotbetennelse (U.S. 5000886). I anordningen inngår en smal spisseksjon som er tilstrekkelig liten til å innføres i rothinnelommen. Det pulveriserte, terapeutiske middel er plassert i en trang kanal i spissen, og overføres fra spissen til rothinnelommen. To this end, a device and a method for introducing a finely powdered, solid and antibiotic therapeutic agent into the root membrane pocket of a patient suffering from tooth root inflammation has recently been provided (U.S. 5000886). The device includes a narrow tip section that is sufficiently small to be introduced into the root membrane pocket. The powdered therapeutic agent is placed in a narrow channel in the tip, and is transferred from the tip to the root membrane pocket.
Det har vist seg å være vanskelig å fylle den trange kanal i den periodontiske dispenseranordning med den riktige mengde av det pulveriserte, terapeutiske middel, på grunn av den lille åpning hvorigjennom middelet må innføres, og det relativt lange og trange hulrom som må fylles. På grunn av at en standarddose av det terapeutiske middel må overføres til rothinnelommen, må dessuten dispenseranordningen fylles på nøyaktig og gjentatt måte. It has proven difficult to fill the narrow channel of the periodontic dispensing device with the correct amount of the powdered therapeutic agent, due to the small opening through which the agent must be introduced, and the relatively long and narrow cavity that must be filled. In addition, because a standard dose of the therapeutic agent must be transferred to the root canal pocket, the dispensing device must be filled accurately and repeatedly.
Ved en kjent fremgangsmåte for fylling av en sylinder, eksempelvis en pat-ron, med et pulvermateriale såsom krutt, anbringes kruttet i en trakt, for å viderefø-res under tyngdekraftpåvirkning gjennom trakthalsen og inn i patronen. Denne fremgangsmåte er ikke egnet for fylling av den ovennevnte, periodontiske dispenseranordning, fordi hulrommet som skal fylles, er for trangt til at partiklene kan strømme inn ved falltilførsel. Det terapeutiske middel er dessuten hydroskopisk, og vil ikke strømme jevnt. In a known method for filling a cylinder, for example a cartridge, with a powder material such as gunpowder, the gunpowder is placed in a funnel, to be carried on under the influence of gravity through the funnel neck and into the cartridge. This method is not suitable for filling the above-mentioned periodontic dispensing device, because the cavity to be filled is too narrow for the particles to flow in by drop feeding. The therapeutic agent is also hydroscopic, and will not flow smoothly.
Et langt og trangt hulrom, f.eks. kanalen i den periodontiske dispenseranordning, kan fylles på en annen måte ved at pulveret samles i en haug, hvoretter kanalen innskyves gjentatte ganger i haugen, til dispenserens tyngde er øket med tyngden av den ønskede medikamentmengde. Denne fremgangsmåte er imidlertid ytterst tidkrevende og unøyaktig. A long and narrow cavity, e.g. the channel in the periodontic dispenser device can be filled in another way by collecting the powder in a pile, after which the channel is pushed repeatedly into the pile, until the weight of the dispenser has been increased by the weight of the desired amount of medication. However, this method is extremely time-consuming and inaccurate.
Det er derfor et formål ved oppfinnelsen å frembringe en anordning som er egnet for fylling av et langt og smalt hulrom med relativt liten åpning med et finpulverisert materiale. Et annet formål ved oppfinnelsen er å frembringe en anordning som er egnet for nøyaktig fylling av et langt og smalt hulrom i en anordning for ut-deling av slikt materiale, med en enhetsdose av et farmakologisk aktivt pulvermateriale. It is therefore an object of the invention to produce a device which is suitable for filling a long and narrow cavity with a relatively small opening with a finely powdered material. Another object of the invention is to produce a device which is suitable for accurately filling a long and narrow cavity in a device for dispensing such material, with a unit dose of a pharmacologically active powder material.
Disse formål oppnås ifølge oppfinnelse ved en anordning som angitt i det etterfølgende krav 1. Fordelaktige utføringsformer er angitt i krav 2-5. Oppfinnelsen omfatter også en fremgangsmåte for fylling av et hulrom som har en åpning med et fint pulverisert materiale, som angitt i det etterfølgende krav 6. These purposes are achieved according to the invention by a device as stated in the following claim 1. Advantageous embodiments are stated in claims 2-5. The invention also includes a method for filling a cavity which has an opening with a finely powdered material, as stated in the following claim 6.
Anordningen innbefatter således en utløpsport med en munning som er slik plassert at den er rettet mot åpningen av hulrommet som skal fylles, men adskilt gjennom et mellomrom fra åpningen av hulrommet, midler som holder det finpulveriserte materiale svevende i en gjennomløpende gassstrøm og for utstøting av gasstrømmen gjennom utløpsportens munning, hvorved pulveret, når gassen med innhold av det svevende pulvermateriale utstøtes gjennom utløpsportmunningen, vil utjevne mellomrommet og fylle hulrommet, mens gassen unnviker gjennom mellomrommet. Spalten mellom utløpsporten og åpningen av hulrommet som skal fylles, bør ikke overstige det dobbelte av utløpsportmunningens størrelse og fortrinnsvis tilsvare ca. 0,2 - 2 ganger størrelsen av nevnte munning. Da pulverets densitet vanligvis er mange ganger større enn gassens, kan gassen lett endre retning og unnvike gjennom spalten mens pulveret derimot, på grunn av sin større tetthet, opprettholder sin bevegelsesretning, grunnet sin treghet, gjennom det lange og smale hulrom. Den bortre ende av hulrommet som skal fylles, må være gjentettet. Hvis anordningene som skal fylles, er i form av piper eller rør av liten størrelse, kan den bortre ende avtettes midlertidig, til ifyllingen er fullført. Når hulrommet er helt oppfylt, vil det overskytende pulver automatisk utstrømme gjennom spalten, og kan om ønskelig tilbakeføres. Ifølge oppfinnelsen skal slikt pulver til-bakeføres, fordi det er et verdifullt, farmasøytisk produkt som det må gjøres rede for. The device thus includes an outlet port with a mouth positioned to face the opening of the cavity to be filled but separated by a space from the opening of the cavity, means for keeping the finely powdered material suspended in a passing gas stream and for ejecting the gas stream through the outlet port mouth, whereby the powder, when the gas containing the suspended powder material is expelled through the outlet port mouth, will equalize the space and fill the cavity, while the gas escapes through the space. The gap between the outlet port and the opening of the cavity to be filled should not exceed twice the size of the outlet port mouth and preferably correspond to approx. 0.2 - 2 times the size of said mouth. As the density of the powder is usually many times greater than that of the gas, the gas can easily change direction and escape through the gap, while the powder, on the other hand, due to its greater density, maintains its direction of movement, due to its inertia, through the long and narrow cavity. The far end of the cavity to be filled must be resealed. If the devices to be filled are in the form of pipes or tubes of small size, the far end can be temporarily sealed until the filling is complete. When the cavity is completely filled, the excess powder will automatically flow out through the gap, and can be returned if desired. According to the invention, such powder must be returned, because it is a valuable pharmaceutical product that must be accounted for.
Det henvises til de medfølgende tegninger, hvori: Reference is made to the accompanying drawings, in which:
Figur 1 viser utløpsporten, mellomrommet og hulrommet som skal fylles. Figure 1 shows the outlet port, the gap and the cavity to be filled.
Figur 2 viser et blokkdiagram av systemets kontrollelementer. Figure 2 shows a block diagram of the system's control elements.
Figur 3 viser en versjon av fylleanordningen ifølge oppfinnelsen. Figure 3 shows a version of the filling device according to the invention.
Figur 4 viser et detaljert riss av dyseenhetens manifold. Figure 4 shows a detailed view of the nozzle assembly manifold.
Figur 5 viser et detaljert riss av dysehuset. Figure 5 shows a detailed view of the nozzle housing.
Figur 6 viser en dispenser som fylles ved hjelp av anordningen ifølge oppfinnelsen. Figur 7 viser et histogram av ifyllingsvekter for et farmasøytisk pulver, hvor den ønskede ifyllingsvekt er 4,5 mg. Figur 8 viser en flerenhetsdose-pulverdispenser av en type for anvendelse ved medikamenter som kan overføres ved oral inhalering. Figur 9 viser en annen versjon av fylleanordningen ifølge oppfinnelsen. Figure 6 shows a dispenser that is filled using the device according to the invention. Figure 7 shows a histogram of filling weights for a pharmaceutical powder, where the desired filling weight is 4.5 mg. Figure 8 shows a multi-unit dose powder dispenser of a type for use with drugs that can be transferred by oral inhalation. Figure 9 shows another version of the filling device according to the invention.
Fylleanordningen ifølge oppfinnelsen er særlig egnet for ifylling av et finpulverisert materiale i et langt og smalt hulrom med en relativt liten åpning. I forbindelse med oppfinnelsen betyr "smalt" en bredde eller diameter av ca. 1 mm eller mindre og "langt" en lengde av ca. 7 mm. Hulrommet som skal fylles, kan ha hvilken som helst tverrsnittsform, såsom kvadratisk, rektangulær, sfærisk eller uregel-messig. Hulrommet behøver ikke å ha ensartet tverrsnittsform. I forbindelse med oppfinnelsen er "relativt liten åpning" ment å angi en åpningsbredde eller-diameter av ca. 1 mm eller mindre. I likhet med hulrommet kan åpningen ha forskjellige former. The filling device according to the invention is particularly suitable for filling a finely powdered material into a long and narrow cavity with a relatively small opening. In connection with the invention, "narrow" means a width or diameter of approx. 1 mm or less and "long" a length of approx. 7 mm. The cavity to be filled can have any cross-sectional shape, such as square, rectangular, spherical or irregular. The cavity does not need to have a uniform cross-sectional shape. In connection with the invention, "relatively small opening" is intended to indicate an opening width or diameter of approx. 1 mm or less. Like the cavity, the opening can have different shapes.
Oppfinnelsen er særlig egnet for fylling av ulike dispenseranordninger for tildeling av enhetsdoseformer av farmakologisk aktive materialer. Det bør i dette øyemed bemerkes at materialet må pakkes i dispenseranordningens hulrom på slik måte at det kan avgis fra hulrommet. Anordningen ifølge oppfinnelsen er unikt egnet for slik ifylling, fordi de pulveriserte materialer ikke pakkes for fast, fordi materialene transporteres i en fremløpende gasstrøm. I denne forbindelse bør det videre bemerkes at sylindriske kamre er særlig egnet for å fylles ved hjelp av anordningen ifølge oppfinnelsen, fordi sylindriske løp og sylindriske trykkstempler gir reproduserbare tverrsnitt og mengder for tildeling. Videre er sylindriske trykkstempler velegnet for avgiving av hele materialmengden, uten at noe etterlates i hjørner etc. Hvis et hulrom har mer enn én åpning, bør samtlige bortsett fra én enkelt gjentettes midlertidig under ifyllingen, da den partikkelfylte gasstrøm ellers vil utløpe gjennom de andre åpninger, slik at hulrommet ikke fylles. Denne midler-tidige avtetning kan lettvint fjernes og gjenstander såsom små rør eller piper fylles. The invention is particularly suitable for filling various dispenser devices for the allocation of unit dose forms of pharmacologically active materials. In this regard, it should be noted that the material must be packed in the cavity of the dispenser device in such a way that it can be emitted from the cavity. The device according to the invention is uniquely suitable for such filling, because the powdered materials are not packed too tightly, because the materials are transported in an advancing gas stream. In this connection, it should further be noted that cylindrical chambers are particularly suitable for filling by means of the device according to the invention, because cylindrical barrels and cylindrical pressure pistons provide reproducible cross-sections and quantities for allocation. Furthermore, cylindrical pressure pistons are suitable for dispensing the entire amount of material, without leaving anything in corners etc. If a cavity has more than one opening, all but one should be temporarily resealed during filling, as the particle-filled gas stream will otherwise escape through the other openings , so that the cavity is not filled. This temporary seal can be easily removed and objects such as small pipes or pipes filled.
Fylleanordningen ifølge oppfinnelsen er særlig egnet for fylling av samtlige typer av finpulveriserte og faste, eksempelvis farmakologisk aktive pulvermateria- ler. Av de farmakologisk aktive midler som kan finpulveriseres og derfor er egnet for å ifylles ved hjelp av anordningen ifølge oppfinnelsen, kan nevnes peptider og proteiner. Spesielle eksempler på sistnevnte omfatter natriuretisk luftfaktor, tumo-rnekrosefaktor, oksytosin, vasopresin, adrenkortisotropisk hormon (ACTH), epi-demisk vekstfaktor, tryosidiner, gramisidiner, renin, bradykinin, angitensiner, enk-torfiner, enkefaliner, kalsitonin, lakskalsitonin, sekretin, kalsitoninbeslektet gene-faktor, vevplasminogenfaktor, nyreplasminogenfaktor, kolecystokinin, melanocyt-forebyggende faktor, melanocytstimulerende hormon, nevropeptid y, nervevekst-faktor, muramyldipeptid, timopoietin, menneskelig veksthormon, procinveksthor-mon, natriumpentemedin, bovinveksthormon, insulin, tyrotropinutløsende hormon (TRH), arogastron, pentagastrin, tetragastrin, gastrin, interferoner, glukagon, somatostatin, prolaktin, superoksiddismutose, luteiniserende hormonutløsende hormon (LHRH), H-5-Oxo-Pro-His-Trp-Ser-Tyr-DTrp-Leu-Arg-Pro-GlyNH2, H-5-Oxo-Pro-His-Trp-Ser-Tyr-3-(2Naftyl)-D-alanyl-Leu-Arg-Pro-Gly-NH2)Luteiniserende hormonutløsende faktor (pig), 6-[0-(1,1-dimetyletyl)-D-serin]-10-deglycinamid-2-(aminokarbonyl)hydrasid (9CI), luteiniserende hormonutløsende faktor (pig), 6-[0-1,1-dimetyletyl)-D-serin]-9-[N-etyl-L-prolinamid)-10-deglycinamid (9CI), luteiniserende hormonutløsende faktor (pig), 6-D-leucin-9-(N-etyl-L-prolinamid)-10-deglycinamid-(9CI) og syntetiske analoge og modifikasjoner samt farmalogisk aktive fragmenter av disse og farmasøytisk akseptable salter av samme. The filling device according to the invention is particularly suitable for filling all types of finely powdered and solid, for example pharmacologically active powder materials. Of the pharmacologically active agents which can be finely pulverized and are therefore suitable for filling using the device according to the invention, peptides and proteins can be mentioned. Particular examples of the latter include natriuretic air factor, tumor necrosis factor, oxytocin, vasopressin, adrenocortisotropic hormone (ACTH), epidemic growth factor, tryosidines, gramicidins, renin, bradykinin, angitensins, enk-torphins, enkephalins, calcitonin, laccalcitonin, secretin, calcitonin-related gene factor, tissue plasminogen factor, kidney plasminogen factor, cholecystokinin, melanocyte-preventive factor, melanocyte-stimulating hormone, neuropeptide y, nerve growth factor, muramyl dipeptide, thymopoietin, human growth hormone, procin growth hormone, pentemedine sodium, bovine growth hormone, insulin, thyrotropin-releasing hormone (TRH), arogastron, pentagastrin, tetragastrin, gastrin, interferons, glucagon, somatostatin, prolactin, superoxide dismutosis, luteinizing hormone-releasing hormone (LHRH), H-5-Oxo-Pro-His-Trp-Ser-Tyr-DTrp-Leu-Arg-Pro-GlyNH2, H -5-Oxo-Pro-His-Trp-Ser-Tyr-3-(2Naphthyl)-D-alanyl-Leu-Arg-Pro-Gly-NH2)Luteinizing hormone-releasing factor (pig), 6-[0-(1, 1-dimethylethyl)-D-ser in]-10-deglycinamide-2-(aminocarbonyl)hydrazide (9CI), luteinizing hormone-releasing factor (pig), 6-[0-1,1-dimethylethyl)-D-serine]-9-[N-ethyl-L- prolinamide)-10-deglycinamide (9CI), luteinizing hormone-releasing factor (pig), 6-D-leucine-9-(N-ethyl-L-prolinamide)-10-deglycinamide-(9CI) and synthetic analogues and modifications as well as pharmacologically active fragments thereof and pharmaceutically acceptable salts thereof.
Andre klasser av sammensetninger som er egnet for å ifylles ved hjelp av anordningen ifølge oppfinnelsen omfatter peniciliner, betalaktamaseinhibitorer, cefalosporiner, kvinoloner, aminoglycosidantibiotika (gentamicin, tobramycin, ka-namycin, amikacin), estradiol, noretisteron, noretindron, progesteron, testosteron, amcinonid, akromycin, tetracykliner (doksycyklin, minocyklin, oksytetracyklin, te-tracyklin, klortetracyklin, demeklocyklin, metacylin), clindamycin, Vitamin B-12, anestetika (prokain, tetrakain, lidokain, mepivakain, etidokain), mitoksantron, bi-santren, doksorubicin, mitomycin C, blemycin, vinblastin, vinkristin, cytosin ara-bidosid, ARA-AC, aktinomycin D, daunmycin, daunomycin benzoylhydrason, nitro-gensenneper, 5-azacytidin, kalsium leukovorin, cis-platinaforbindelser, 5-fluoracil, metotreksat, aminopterin, maytansin, melfalan, mekaptopuriner, metyl CCNU, heksametylmelamin, etoposid, hydroksylurea, levamisol, mitokvanson, misonida-sol, pentostatin, teniposid, tiokvanin, diklormetotreksat, klorprotiksen, molindon, lokapin, haloperidol, klorpromasin, triflupromasin, mesoridasin, tioridasin, flufena- sin, perfenasin, trifluperasin, tiotiksen, og farmasøytisk akseptable salter av ovennevnte, hydromorfon, oksymorfon, levorfenol, hydrokodon, okskodon, nalofin, na-lokson, naltrekson, buprenorfin, butorfenol, nalbufin, mefidin, alfaprodin, anileridin, dipenoksylat, fentanyl og farmasøytisk akseptable salter av de ovennevnte. Disse kan anvendes i finpulverisert form, ved partikkelstørrelser av ca. 0,5 mikron eller mer. Det påpekes imidlertid at materialenes partikkeldimensjon ikke må være så stor at den vil forhindre suspendering i en fremløpende gass-strøm. I de egnede materialer inngår også mikroinnkapslede, farmasøytiske produkter av den type som er kjent fra US-5 000 886. Slike materialer har typisk diameterstørrelse av 20-120 mikron, og er derfor egnet for å ifylles ved hjelp av anordningen ifølge oppfinnelsen. Other classes of compositions suitable for filling by means of the device according to the invention include penicillins, beta-lactamase inhibitors, cephalosporins, quinolones, aminoglycoside antibiotics (gentamicin, tobramycin, kanamycin, amikacin), estradiol, norethisterone, norethindrone, progesterone, testosterone, amcinonide, acromycin, tetracyclines (doxycycline, minocycline, oxytetracycline, tetracycline, chlortetracycline, demeclocycline, methacycline), clindamycin, Vitamin B-12, anesthetics (procaine, tetracaine, lidocaine, mepivacaine, etidocaine), mitoxantrone, bisantren, doxorubicin, mitomycin C, blemycin, vinblastine, vincristine, cytosine arabidoside, ARA-AC, actinomycin D, daunmycin, daunomycin benzoylhydrazone, nitro gen mustard, 5-azacytidine, calcium leucovorin, cis-platinum compounds, 5-fluoroacil, methotrexate, aminopterin, maytansine, melphalan, mecaptopurines, methyl CCNU, hexamethylmelamine, etoposide, hydroxylurea, levamisole, mitoquanson, misonida-sol, pentostatin, teniposide, thioquanine, dichlormethotrexate, chlorprothixene, molindone, locapine, haloperidol, chlorpromazine, triflupromazine, mesoridazine, thioridazine, fluphenazine, perphenazine, trifluperazine, thiothixene, and pharmaceutically acceptable salts of the above, hydromorphone, oxymorphone, levorphenol, hydrocodone, oxcodone, nalofin, naloxone , naltrexone, buprenorphine, butorphenol, nalbuphine, mefidine, alphaprodine, anileridine, dipenoxylate, fentanyl and pharmaceutically acceptable salts of the above. These can be used in finely powdered form, with particle sizes of approx. 0.5 micron or more. It is pointed out, however, that the particle size of the materials must not be so large that it will prevent suspension in an advancing gas stream. The suitable materials also include microencapsulated pharmaceutical products of the type known from US-5 000 886. Such materials typically have a diameter of 20-120 microns, and are therefore suitable for filling using the device according to the invention.
Det bør bemerkes at den type av gass som benyttes for å holde fastmate-rialpartiklene i svevende tilstand, må være forenelig med materialet og dessuten, hvis det er tale om farmasøytiske produkter, oppfylle de sanitære krav. I denne forbindelse og under iakttagelse av forenelighet og sanitære krav, er det tatt i be-traktning at mange forskjellige gasser kan anvendes, deriblant luft, nitrogen, tørr-luft, karbondioksid, argon og andre inærte gasser. Tørr luft eller nitrogen vil foretrekkes i forbindelse med hydroskopiske eller hydrofile partikler. It should be noted that the type of gas used to keep the solid material particles in suspension must be compatible with the material and, in the case of pharmaceutical products, also meet the sanitary requirements. In this connection and while observing compatibility and sanitary requirements, it has been taken into account that many different gases can be used, including air, nitrogen, dry air, carbon dioxide, argon and other inert gases. Dry air or nitrogen will be preferred in connection with hydroscopic or hydrophilic particles.
Som det fremgår av figur 1, er en utløpsport 1 med en munning 4 og av en bredde eller diameter D slik plassert, at den er rettet mot en åpning 5 i dispenseranordningen 3 som har et hulrom 2. Åpningen 5 har en bredde eller diameter X. Utløpsporten 1 er gjennom en spalte G adskilt fra hulromåpningen 5. Bredden eller diameteren D av utløpsportmunningen 4 må være lik eller mindre enn bredden eller diameteren X av åpningen 5 av hulrommet 2, for å fylles. I visse tilfeller, eksempelvis ved utløpsportåpninger eller hulromåpninger av irregulære eller forskjellige former, vil det være ønskelig at utløpsporten er innpassbar i hulromåpningen. Hvis bredden eller diameteren av utløpsportmunningen 4 overstiger bredden eller diameteren X av hulrommet 2, vil en stor del av partikkelmaterialet som er suspendert i gasstrømmen, ledes forbi siden av anordningen 3 og ikke inntrenge i hulrommet 2. Munningen 4 av utløpsporten 1 og åpningen 5 i anordningen 3 er adskilt i en avstand som bestemmes av spalten G. Det har vist seg at en spalte som ikke overstiger to ganger bredden eller diameteren D av munningen 4, vil væ-re passende. Det foretrekkes at spalten G tilsvarer 0,2 - 2 ganger bredden eller diameteren D. Spalten G må være tilstrekkelig stor, slik at gass kan unnvike, men ikke så stor at partikkelmaterialet ikke vil medføres i gasstrømmen og utjevne spalten. As can be seen from figure 1, an outlet port 1 with a mouth 4 and of a width or diameter D is positioned so that it is directed towards an opening 5 in the dispenser device 3 which has a cavity 2. The opening 5 has a width or diameter X The outlet port 1 is separated from the cavity opening 5 by a gap G. The width or diameter D of the outlet port mouth 4 must be equal to or less than the width or diameter X of the opening 5 of the cavity 2, in order to be filled. In certain cases, for example with outlet port openings or cavity openings of irregular or different shapes, it will be desirable that the outlet port can be fitted into the cavity opening. If the width or diameter of the outlet port mouth 4 exceeds the width or diameter X of the cavity 2, a large part of the particulate material suspended in the gas flow will be led past the side of the device 3 and not enter the cavity 2. The mouth 4 of the outlet port 1 and the opening 5 in the device 3 is separated by a distance determined by the gap G. It has been found that a gap not exceeding twice the width or diameter D of the orifice 4 will be suitable. It is preferred that the gap G corresponds to 0.2 - 2 times the width or diameter D. The gap G must be sufficiently large, so that gas can escape, but not so large that the particulate material will not be entrained in the gas flow and equalize the gap.
I den versjon av anordningen som er beskrevet i tilknytning til figur 2-4, har utløpsportmunningen en diameter av 0,96 mm og spalten er 0,25 mm. In the version of the device described in connection with Figures 2-4, the outlet port mouth has a diameter of 0.96 mm and the gap is 0.25 mm.
Det påpekes at det pulveriserte materiale kan suspenderes i en fremløpen-de gasstrøm ved anvendelse av et vilkårlig antall anordninger, slik som den ven-turianordning som er mer detaljert beskrevet, eller et fluidisert sjikt eller enhver annen anordning som vil bevirke suspendering av materialpartikler i en fremlø-pende gasstrøm. Den spesielle anordning må imidlertid kunne suspendere partikler i tilstrekkelig mengde til å fylle de nødvendige hulrom hurtig og effektivt, men uten at det suspenderes for mange partikler som vil kunne gjentette utløpsporten eller spalten. I denne forbindelse kan f.eks. gassens strømningshastighet gjennom en anordning, f.eks. en venturi, reguleres med henblikk på riktig suspendering av partikler i gasstrømmen. It is pointed out that the pulverized material can be suspended in an advancing gas stream using any number of devices, such as the venturi device described in more detail, or a fluidized bed or any other device that will effect suspension of material particles in a forward gas flow. However, the special device must be able to suspend particles in a sufficient amount to fill the necessary cavities quickly and efficiently, but without suspending too many particles that could clog the outlet port or slot. In this connection, e.g. the flow rate of the gas through a device, e.g. a venturi, is regulated with a view to the correct suspension of particles in the gas stream.
I en versjon omfatter fylleanordningen en beholder for oppbevaring av pulvermaterialet som skal ifylles, en gasskilde (fortrinnsvis tørr luft eller nitrogen), en regulator for opprettelse av den nødvendige strømningsmengde, en venturi-dyseenhet for utstøting av gassen og innsuging av pulveret i gassutløpsstrømmen. Om ønskelig kan det også anordnes en overløpsoppsamler for oppfanging av den pulver-overskuddsmengde som kreves for fylling av den trange kanal. In one version, the filling device comprises a container for storing the powder material to be filled, a gas source (preferably dry air or nitrogen), a regulator for creating the required flow rate, a venturi nozzle unit for ejecting the gas and sucking the powder into the gas outlet stream. If desired, an overflow collector can also be arranged to collect the excess amount of powder required for filling the narrow channel.
Som vist i figur 2, blir en gasskilde 10 regulert med en regulator 15, innen den forbindes med en solenoidestyrt, pneumatisk ventil 20. Når den pneumatiske ventil 20 opplades ved hjelp av en 115 volt spenningskilde 25 av standard type, åpnes en solenoidestyrt ventil, slik at gassen kan strømme gjennom et rør 30 til fyllesystemet. Da det for drift av anordningen ifølge oppfinnelsen bare kreves en kortvarig gasstilstrømning, innstilles et justerbart tidsrelé 35 for begrensing av den solenoidestyrte, pneumatiske ventils åpningstidsrom til under ett sekund. Selv om det ikke er nødvendig, vil det foretrekkes at gasstilførselen pulserer, for å unngå pakking av det finpulveriserte materiale. Lukkingen av tidsreléet 35 innledes ved betjening av en lukker-fotbryter 40. As shown in Figure 2, a gas source 10 is regulated by a regulator 15 before being connected to a solenoid operated pneumatic valve 20. When the pneumatic valve 20 is charged by a standard type 115 volt voltage source 25, a solenoid operated valve is opened, so that the gas can flow through a pipe 30 to the filling system. Since for the operation of the device according to the invention only a short-term gas inflow is required, an adjustable time relay 35 is set to limit the opening time of the solenoid-controlled, pneumatic valve to less than one second. Although it is not necessary, it would be preferable for the gas supply to pulse, to avoid packing of the finely powdered material. The closing of the time relay 35 is initiated by operating a shutter foot switch 40.
Fyllesystemet er vist mer detaljert i figur 3. Gasstilførselen til systemet 30 er vist både i figur 3 og 2. Gasstilførselen er gjennom en pneumatisk kopling 50 av standard type forbundet med venturidyseenheten 45. I dyseenheten 45 strømmer inn gassen i en manifold 55 som er vist både i figur 3 og 4. Som det fremgår av figur 4, er det gjennom manifolden innført et pulvertilførselsrør 60 som fungerer som støttekonstruksjon for manifoldmontasjen. En flens 65 gjør det mulig for gassen å strømme inn i manifoldmontasjen gjennom en utsparing 70, passere gjennom et overtrykkskammer 75 og utstrømme gjennom åpninger 80 i en hull-plate 85. Gassen vil på denne måte utstrømme gjennom flere åpninger, og om-slutte pulvertilførselsrøret 60. The filling system is shown in more detail in Figure 3. The gas supply to the system 30 is shown in both Figures 3 and 2. The gas supply is through a pneumatic coupling 50 of a standard type connected to the venturi nozzle unit 45. In the nozzle unit 45, the gas flows into a manifold 55 which is shown both in Figures 3 and 4. As can be seen from Figure 4, a powder supply pipe 60 has been introduced through the manifold which functions as a support structure for the manifold assembly. A flange 65 enables the gas to flow into the manifold assembly through a recess 70, pass through an overpressure chamber 75 and flow out through openings 80 in a perforated plate 85. The gas will thus flow out through several openings, enclosing the powder supply pipe 60.
Figur 3 viser at gasstilførselsrøret 30 forgrenes i en T-kopling 90 og fort-setter både til dysemontasjen 45 og til pulverforrådet 95 og, nærmere bestemt, til rommet 100 over pulveret. Ved den pulserende virkemåte hvorved pulverforrådet bringes under trykk, vil pulveravgivingen innledes meget hurtig. Uten dette "på-skynd ingstrykk" vil det gå flere sekunder innen venturivirkningen kan frembringe nyttig pulverstrøm. Et sugerør 110 er nedført i pulveret 105 og strekker seg til manifoldmontasjen og inn i dyseenheten 45. Figure 3 shows that the gas supply pipe 30 branches off in a T-connection 90 and continues both to the nozzle assembly 45 and to the powder supply 95 and, more specifically, to the space 100 above the powder. With the pulsating mode of operation by which the powder supply is brought under pressure, the powder delivery will begin very quickly. Without this "acceleration pressure", several seconds will pass before the venturi effect can produce useful powder flow. A suction pipe 110 is lowered into the powder 105 and extends to the manifold assembly and into the nozzle unit 45.
Et dysehus 115 er vist i figur 5. Den tilførte gass strømmer inn gjennom en sylindrisk åpning 120, og manifolden er innført gjennom en åpning 125. Den trange sylinderkanal som skal fylles, innplasseres i en sylindrisk holderinnretning 130, og den eventuelt overskytende pulvermengde vil avledes gjennom en overløps-ledning 135. A nozzle housing 115 is shown in Figure 5. The supplied gas flows in through a cylindrical opening 120, and the manifold is introduced through an opening 125. The narrow cylinder channel to be filled is placed in a cylindrical holder device 130, and any excess powder quantity will be diverted through an overflow line 135.
Når anordningen er i bruk blir gassen, etter å ha forlatt dysen 80, tvunget til å strømme gjennom en konisk avsmalnende venturisone 140 som dannes av kla-ringen mellom manifolden og pulvertilførselsledningen 60. Fordi gasshastigheten er høy gjennom venturien 140, blir trykket i denne sone meget redusert. When the device is in use, the gas, after leaving the nozzle 80, is forced to flow through a conically tapered venturi zone 140 formed by the clearance between the manifold and the powder supply line 60. Because the gas velocity is high through the venturi 140, the pressure in this zone greatly reduced.
Denne lavtrykkssone bevirker at pulveret 105 nedføres gjennom sugerøret 110 og blandes med gassen, hvoretter gass/pulverblandingen utstrømmer gjennom en utløpsport 131. Under drift, som vist i figur 3, vil dispenseranordningen med et hulrom 145 som skal fylles, fastholdes i en holderinnretning 130 i dysehuset 115. This low-pressure zone causes the powder 105 to be brought down through the suction tube 110 and mixed with the gas, after which the gas/powder mixture flows out through an outlet port 131. During operation, as shown in Figure 3, the dispenser device with a cavity 145 to be filled will be retained in a holder device 130 in nozzle housing 115.
Spalten G er kritisk for virkemåten av denne anordning. Gjennom over-løpsledningen 135 kan overskuddsgass og -pulvermateriale avledes under ifyl-lingsprosessen. Under drift vil pulveret pakkes i hulrommet i dispenseranordningen 145 grunnet hastigheten av gass/pulverblandingen, men gassen av meget lavere densitet kan endre retning og utstrømme gjennom spalten G og overløps-ledningen 135. Column G is critical to the operation of this device. Through the overflow line 135, excess gas and powder material can be diverted during the filling process. During operation, the powder will be packed into the cavity in the dispenser device 145 due to the speed of the gas/powder mixture, but the gas of much lower density can change direction and flow out through the gap G and the overflow line 135.
En viss pulvermengde vil blandes med overskuddsgassen og medføres inn i overløpsoppsamleren 150. For å unngå trykkøkning i overløpsoppsamleren 150 er det anordnet et utløp 155 til ytterluften. Hvis beholderen 150 for oppsamling av overløpet ikke hadde luftutløp til atmosfæren, ville trykket øke i beholderen. Dette trykk ville øke, til det nådde samme størrelse som drivgasstrykket. På dette stadi-um vil det ikke eksistere trykkforskjell og følgelig ingen drivkraft. For å unngå at det omgivende miljø forurenses av pulver som ifylles, er det i overløpsoppsamle-ren anordnet et filter 160 som skal hindre pulveret i å unnvike og dessuten gjen-vinne pulveret i de tilfeller hvor pulvermaterialet er verdifullt. A certain amount of powder will be mixed with the excess gas and carried into the overflow collector 150. To avoid a pressure increase in the overflow collector 150, an outlet 155 to the outside air is arranged. If the container 150 for collecting the overflow did not have an air outlet to the atmosphere, the pressure would increase in the container. This pressure would increase, until it reached the same magnitude as the propellant gas pressure. At this stage, there will be no pressure difference and consequently no driving force. In order to prevent the surrounding environment from being contaminated by powder that is filled in, a filter 160 is arranged in the overflow collector which will prevent the powder from escaping and also recover the powder in cases where the powder material is valuable.
En dispenser 200 som er vist i figur 6, består av to deler, en sylinder 210 og et trykkstempel 220. I en foretrukket versjon kan dispenseren oppta et farmasøy-tisk aktivt materiale i en nøyaktig tilmålt mengde av 4,5 mg. Et modifisert dybde-mikrometer 230 er innmontert i en blokk 240, slik at når mikrometetrrommelen dreies vil en derved forbundet tapp 235 beveges innad eller utad, avhengig av mikrometetrrommelens rotasjonsretning. Tappen 235 er dimensjonert for lett å kunne innpasses i dispensersylinderen 210. Under bruk inntrykkes stempelet 220 og dispenseranordningen innskyves på tappen 235, for innstilling av en fast og gjentakbar plassering av stempelet 220 i sylinderen 210. Hvis materialmengden som skal tilmåles, alltid er fiksert, er mikrometerjustering unødvendig og kan er-stattes av en tapp av fast lengde. A dispenser 200 shown in figure 6 consists of two parts, a cylinder 210 and a pressure piston 220. In a preferred version, the dispenser can receive a pharmaceutical active material in a precisely measured amount of 4.5 mg. A modified depth micrometer 230 is fitted in a block 240, so that when the micrometer drum is rotated, a pin 235 connected to it will be moved inward or outward, depending on the direction of rotation of the micrometer drum. The pin 235 is dimensioned to easily fit into the dispenser cylinder 210. During use, the piston 220 is pressed in and the dispensing device is pushed onto the pin 235, to set a fixed and repeatable position of the piston 220 in the cylinder 210. If the amount of material to be measured is always fixed, micrometer adjustment is unnecessary and can be replaced by a spigot of fixed length.
Utførelsesformen som er vist i figur 1-6, er evaluert med henblikk på riktig og nøyaktig fylling av hulrommet 250 i dispenseren 200. Figur 6 viser et typisk histogram av ifyllingsvekter eller tilnærmelsesvis 5400 ifyllinger. The embodiment shown in Figures 1-6 has been evaluated for correct and accurate filling of the cavity 250 in the dispenser 200. Figure 6 shows a typical histogram of fill weights or approximately 5400 fills.
Histogrammets X-akse angir ifyllingsvektene av 5400 rothinne-dispensere som er fylt med antibiotisk minocyklin. De resulterende ifyllingsvekter er av frem-stillingsgrunner fordelt i 14 beholdere i mengder av 3,9 - 5,2 mg med et sprang på 0,1 mg. Histogrammets Y-akse angir antallet dispensere med den indikerte ifyllingsvekt. The X-axis of the histogram indicates the fill weights of 5400 root membrane dispensers filled with the antibiotic minocycline. For production reasons, the resulting filling weights are divided into 14 containers in quantities of 3.9 - 5.2 mg with a leap of 0.1 mg. The Y-axis of the histogram indicates the number of dispensers with the indicated filling weight.
Som det fremgår, er ifyllingsvekten tett gruppert. Særlig er middel-ifyllingsvekten 4,5 mg (som ønsket) med 0,19 mg standardavvik. Dette 4,22% standardavvik er akseptabelt for farmasøytiske anvendelser. As can be seen, the filling weight is closely grouped. In particular, the mean filling weight is 4.5 mg (as desired) with a standard deviation of 0.19 mg. This 4.22% standard deviation is acceptable for pharmaceutical applications.
Den beskrevne anordning kan også benyttes for fylling av andre medika-mentoverføringsanordninger som skal avgi inhaleringsmidler i pulverform til lun-gen. Særlig er visse medikamenter mest effektiv når de overføres direkte til pasi- entens lunger. Som eksempler kan nevnes medisiner mot reversible luftveihind-ringer, såsom astma, medisiner for kontrahering av lungesykdommer eller-infek-sjoner, legemidler til bekjemping av leilighetsvise lungeinfeksjoner som kan smitte pasienter med antistoffer for HIV-virus (AIDS). Eksemplene innbefatter også poly-peptide produkter av bioteknologi. The device described can also be used for filling other medication transfer devices which are to deliver inhalants in powder form to the lungs. In particular, certain drugs are most effective when they are transferred directly to the patient's lungs. As examples can be mentioned medicines for reversible respiratory obstructions, such as asthma, medicines for contracting lung diseases or infections, medicines for combating occasional lung infections which can infect patients with antibodies for the HIV virus (AIDS). The examples also include poly-peptide products of biotechnology.
Frysetørrede polypeptider kan tildeles ved overføring gjennom luftveiene. Disse rDNA-produkter er meget sterke, og de nødvendige doser vil sannsynligvis være små. Anordningen ifølge oppfinnelsen er egnet for nøyaktig tilmåling av pul-vermedikament i små mengder i en dispenser, for senere bruk. Freeze-dried polypeptides can be administered by transfer through the respiratory tract. These rDNA products are very potent, and the required doses are likely to be small. The device according to the invention is suitable for accurately measuring powder medication in small amounts in a dispenser, for later use.
Figur 8 viser en anordning for lagring av flerdoser av pulvermateriale og egnet for anvendelse i medikamentoverføringsanordninger for avgiving av medikament til lungene. Anordningen omfatter en bæreplate 800, fortrinnsvis av plast-eller papirmateriale med en monteringsinnretning 810 som er vist som et hull men som kan være i form av hvilken som helst, praktisk holderinnretning, og videre med én eller flere lange, tynnrørlignende innretninger 820a-820n som skal inne-holde én eller flere medikamentdoser. Anordningen ifølge oppfinnelsen kan anvendes for fylling av medikament i disse rørlignende innretninger. Innretningen må være fremstilt av et materiale som lett kan gjennomtrenges eller brytes, slik at hele innholdet i én av innretningene kan utnyttes for terapi. Antallet av slike innretninger er valgfritt, men kan uten vanskelighet variere mellom én og tretti doser. Anordningen ifølge oppfinnelsen kan benyttes for fylling av én innretning ad gan-gen, idet den ferdigfylte innretning forsegles, hvoretter bæreplaten 800 dreies ett trinn slik at den etterfølgende innretning 820b blir tilgjengelig for fylleanordningen. Figure 8 shows a device for storing multiple doses of powder material and suitable for use in drug transfer devices for delivering drug to the lungs. The device comprises a carrier plate 800, preferably of plastic or paper material with a mounting device 810 which is shown as a hole but which can be in the form of any practical holding device, and further with one or more long, thin tube-like devices 820a-820n which must contain one or more doses of medication. The device according to the invention can be used for filling medication in these tube-like devices. The device must be made of a material that can be easily penetrated or broken, so that the entire contents of one of the devices can be utilized for therapy. The number of such devices is optional, but can easily vary between one and thirty doses. The device according to the invention can be used for filling one device at a time, the fully filled device being sealed, after which the support plate 800 is turned one step so that the subsequent device 820b becomes accessible to the filling device.
Fylleanordningen ifølge oppfinnelsen kan alternativt være utstyrt med flere venturier samt flere forråd og spalter, slik at samtlige innretninger for platen 800 kan fylles samtidig. The filling device according to the invention can alternatively be equipped with several venturis as well as several stores and slits, so that all devices for the plate 800 can be filled at the same time.
Figur 9 viser en modifisert utførelsesform hvor fylleanordningen ifølge figur 2 er tilpasset for fylling av dispenserinnretningen 820a i stedet for den trange sylinderkanal. Dysehuset 115 er modifisert, idet åpningen 130 som er vist i figur 4, er erstattet av en sliss 900. Bæreplaten 800 kan dreies om en akse 910, slik at innretningene 810a, 810b, 810c osv. plasseres i rekkefølge foran utløpsporten. Figure 9 shows a modified embodiment where the filling device according to Figure 2 is adapted for filling the dispenser device 820a instead of the narrow cylinder channel. The nozzle housing 115 is modified, in that the opening 130 shown in figure 4 is replaced by a slot 900. The support plate 800 can be rotated about an axis 910, so that the devices 810a, 810b, 810c etc. are placed in order in front of the outlet port.
Claims (6)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63245890A | 1990-12-21 | 1990-12-21 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO915073D0 NO915073D0 (en) | 1991-12-20 |
| NO915073L NO915073L (en) | 1992-06-22 |
| NO306937B1 true NO306937B1 (en) | 2000-01-17 |
Family
ID=24535607
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO915073A NO306937B1 (en) | 1990-12-21 | 1991-12-20 | filling device |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP0492088B1 (en) |
| JP (1) | JP3315140B2 (en) |
| KR (1) | KR100227996B1 (en) |
| AR (1) | AR248107A1 (en) |
| AT (1) | ATE128684T1 (en) |
| AU (1) | AU645385B2 (en) |
| CA (1) | CA2058061C (en) |
| DE (1) | DE69113592T2 (en) |
| DK (1) | DK0492088T3 (en) |
| ES (1) | ES2080217T3 (en) |
| FI (1) | FI95117C (en) |
| GR (1) | GR3017652T3 (en) |
| HK (1) | HK1000316A1 (en) |
| IE (1) | IE73431B1 (en) |
| IL (1) | IL99967A (en) |
| NO (1) | NO306937B1 (en) |
| NZ (1) | NZ240793A (en) |
| PT (1) | PT99815B (en) |
| ZA (1) | ZA9110078B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4305879A1 (en) * | 1993-02-26 | 1994-09-01 | Pfeiffer Erich Gmbh & Co Kg | Filling device for filling in magazine chambers |
| DE4446797A1 (en) * | 1994-12-24 | 1996-06-27 | Gema Volstatic Ag | Injector device for the transport of coating powder |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE623721A (en) * | 1961-10-19 | |||
| US3656517A (en) * | 1966-10-20 | 1972-04-18 | Perry Ind Inc | Powder filling machine and method |
| DE1561952A1 (en) * | 1967-08-12 | 1970-04-02 | Allen Transmatik Ltd | Method and device for filling a container with powdery material |
| US3785568A (en) * | 1972-07-05 | 1974-01-15 | E Pfingsten | Particulate material distributing means |
| US4133281A (en) * | 1977-07-20 | 1979-01-09 | Albro Fillers And Engineering Company Ltd. | Vacuum charging of containers from bulk supply |
| DE3145017A1 (en) * | 1981-02-27 | 1982-09-16 | Gustav 8052 Moosburg König | PNEUMATIC CONVEYOR |
-
1991
- 1991-10-31 AT AT91118604T patent/ATE128684T1/en not_active IP Right Cessation
- 1991-10-31 DE DE69113592T patent/DE69113592T2/en not_active Expired - Lifetime
- 1991-10-31 ES ES91118604T patent/ES2080217T3/en not_active Expired - Lifetime
- 1991-10-31 EP EP91118604A patent/EP0492088B1/en not_active Expired - Lifetime
- 1991-10-31 DK DK91118604.7T patent/DK0492088T3/en active
- 1991-11-06 IL IL9996791A patent/IL99967A/en not_active IP Right Cessation
- 1991-11-29 NZ NZ240793A patent/NZ240793A/en not_active IP Right Cessation
- 1991-12-16 PT PT99815A patent/PT99815B/en not_active IP Right Cessation
- 1991-12-17 JP JP35300691A patent/JP3315140B2/en not_active Expired - Lifetime
- 1991-12-19 CA CA002058061A patent/CA2058061C/en not_active Expired - Lifetime
- 1991-12-20 ZA ZA9110078A patent/ZA9110078B/en unknown
- 1991-12-20 IE IE449191A patent/IE73431B1/en not_active IP Right Cessation
- 1991-12-20 AU AU89984/91A patent/AU645385B2/en not_active Expired
- 1991-12-20 FI FI916071A patent/FI95117C/en active IP Right Grant
- 1991-12-20 AR AR91321484A patent/AR248107A1/en active
- 1991-12-20 NO NO915073A patent/NO306937B1/en not_active IP Right Cessation
- 1991-12-21 KR KR1019910023813A patent/KR100227996B1/en not_active IP Right Cessation
-
1995
- 1995-10-05 GR GR950401858T patent/GR3017652T3/en unknown
-
1997
- 1997-10-04 HK HK97101884A patent/HK1000316A1/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| KR920011530A (en) | 1992-07-24 |
| IL99967A (en) | 1994-05-30 |
| AU8998491A (en) | 1992-06-25 |
| ZA9110078B (en) | 1992-10-28 |
| ES2080217T3 (en) | 1996-02-01 |
| KR100227996B1 (en) | 1999-11-01 |
| FI916071A (en) | 1992-06-22 |
| IL99967A0 (en) | 1992-08-18 |
| FI916071A0 (en) | 1991-12-20 |
| FI95117B (en) | 1995-09-15 |
| DE69113592T2 (en) | 1996-05-30 |
| EP0492088B1 (en) | 1995-10-04 |
| ATE128684T1 (en) | 1995-10-15 |
| IE914491A1 (en) | 1992-07-01 |
| CA2058061C (en) | 2002-12-17 |
| NO915073D0 (en) | 1991-12-20 |
| PT99815A (en) | 1994-01-31 |
| HK1000316A1 (en) | 1998-02-27 |
| JPH04327101A (en) | 1992-11-16 |
| FI95117C (en) | 1995-12-27 |
| DE69113592D1 (en) | 1995-11-09 |
| DK0492088T3 (en) | 1995-11-20 |
| EP0492088A1 (en) | 1992-07-01 |
| JP3315140B2 (en) | 2002-08-19 |
| AU645385B2 (en) | 1994-01-13 |
| AR248107A1 (en) | 1995-06-30 |
| GR3017652T3 (en) | 1996-01-31 |
| CA2058061A1 (en) | 1992-06-22 |
| IE73431B1 (en) | 1997-06-04 |
| NZ240793A (en) | 1994-09-27 |
| PT99815B (en) | 1999-02-26 |
| NO915073L (en) | 1992-06-22 |
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| Date | Code | Title | Description |
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| MM1K | Lapsed by not paying the annual fees |