SI9111110A - Process and device for dosing powders - Google Patents
Process and device for dosing powders Download PDFInfo
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- SI9111110A SI9111110A SI9111110A SI9111110A SI9111110A SI 9111110 A SI9111110 A SI 9111110A SI 9111110 A SI9111110 A SI 9111110A SI 9111110 A SI9111110 A SI 9111110A SI 9111110 A SI9111110 A SI 9111110A
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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
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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
- A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
- A61M15/0045—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
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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
- A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
- A61M15/0045—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters
- A61M15/0046—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type of carrier
- A61M15/0051—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type of carrier the dosages being arranged on a tape, e.g. strips
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- 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
- B65B3/00—Packaging plastic material, semiliquids, liquids or mixed solids and liquids, in individual containers or receptacles, e.g. bags, sacks, boxes, cartons, cans, or jars
- B65B3/003—Filling medical containers such as ampoules, vials, syringes or the like
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- 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
- B65B3/00—Packaging plastic material, semiliquids, liquids or mixed solids and liquids, in individual containers or receptacles, e.g. bags, sacks, boxes, cartons, cans, or jars
- B65B3/26—Methods or devices for controlling the quantity of the material fed or filled
- B65B3/34—Methods or devices for controlling the quantity of the material fed or filled by timing of filling operations
- B65B3/36—Methods or devices for controlling the quantity of the material fed or filled by timing of filling operations and arresting flow by cut-off means
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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
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/02—Gases
- A61M2202/0225—Carbon oxides, e.g. Carbon dioxide
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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
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/06—Solids
- A61M2202/064—Powder
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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
- A61M2205/00—General characteristics of the apparatus
- A61M2205/07—General characteristics of the apparatus having air pumping means
- A61M2205/071—General characteristics of the apparatus having air pumping means hand operated
- A61M2205/073—Syringe, piston type
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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
- A61M2205/00—General characteristics of the apparatus
- A61M2205/07—General characteristics of the apparatus having air pumping means
- A61M2205/071—General characteristics of the apparatus having air pumping means hand operated
- A61M2205/075—Bulb type
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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
- A61M2205/00—General characteristics of the apparatus
- A61M2205/82—Internal energy supply devices
- A61M2205/8218—Gas operated
- A61M2205/8225—Gas operated using incorporated gas cartridges for the driving gas
Abstract
Description
Priprava in postopek za doziranje praškovPowder preparation and process
Izum se nanaša na pripravo in postopek za doziranje majhnih količin finih praškov.The invention relates to the preparation and method of dosing small amounts of fine powders.
Majhne količine finih, prednostno mikroniziranih praškov uporabljamo predvsem za terapevtske namene, zlasti v obliki aerosolov za inhalativno zdravljenje obolenj dihalnih poti, kot astme.Small amounts of fine, preferably micronized powders are used primarily for therapeutic purposes, in particular in the form of aerosols for the inhalation of respiratory diseases such as asthma.
Praške te vrste dovajamo v količinah, ki so večinoma razločno pod 50 mg, z dihalnim zrakom v pljuča pacienta. Pri tem se je izkazalo, da morajo imeti delci učinkovine, da pridejo globoko v pljuča velikost pod 10 μτα. To vsekakor ne izključuje uporabo tudi nekoliko bolj grobih delcev v pripravkih, predvsem za morebitne pomožne snovi. Pri uporabi delcev različnih velikosti je razločna razlika v velikosti v danem primeru celo želena ali pač nemoteča; prim. DE-OS 17 92 207.Powders of this type are administered in amounts substantially below 50 mg, with the breathing air into the lungs of the patient. In doing so, it has been shown that the particles have to have the active substance to reach depths below 10 μτα deep into the lungs. This, however, does not preclude the use of slightly coarser particles in the preparations, especially for any of the excipients. When using particles of different sizes, the size difference in the case is even desired or undisturbed; cf. DE-OS 17 92 207.
Za aplikacijo finih praškov brez pomoči poganjalnih plinov pri terapiji dihalne poti sta razviti predvsem dve metodi.In particular, two methods have been developed for the application of fine powders without the aid of propellants in airway therapy.
Ena uporablja kapsule iz trde želatine, ki vsakokrat vsebujejo dozo učinkovine in v danem primeru dodatno pomožne snovi, druga odvzema z merilno komoro določeno količino praška iz vsebnika zaloge in jo primeša dihalnemu zraku. Priprave za obe metodi so v večjem številu opisane, prim. npr. DE-OS 23 46 914; EP-OS 166 294.One uses hard gelatin capsules, each containing a dose of the active ingredient and optionally additional excipients, the other takes a certain amount of powder from the stock container with a measuring chamber and mixes it with the breathing air. Preparations for both methods are described in large numbers, cf. e.g. DE-OS 23 46 914; EP-OS 166 294.
Izum sedaj nudi nov način za aplikacijo finih praškov. Pri njem se povezujeta enostavnost priprave nosilca obloženega z učinkovino s prednostjo natančnega doziranja in možnost, da na enostaven način pripravimo za inhalacijo primeren aerosol.The invention now provides a new way of applying fine powders. It combines the ease of preparation of the active substance-coated carrier with the advantage of accurate dosing and the ability to prepare a suitable aerosol in an easy way for inhalation.
V smislu izuma obložimo velurni ali žameten material s praškom za doziranje in želeno količino praška izpihamo s plinskim curkom, eventualno po mehanskem zrahljanju, prednostno zračnim curkom primerne jakosti iz nosilca. Pri inhalativni uporabi se sproščeni prašek primeša dihalnemu zraku, po želji ob povezavi z inhalacijsko posodo, kot je npr. opisano v nemškem uporabnem vzorcu 89 08273.According to the invention, the velor or velvet material is coated with a dosage powder and the desired amount of powder is blown with a gas jet, possibly after mechanical loosening, preferably air jets of suitable strength from the carrier. In inhalation use, the released powder is mixed with the breath air, optionally in conjunction with an inhalation vessel, such as e.g. described in German utility sample 89 08273.
Pri vtiranju suhega praška v velurni material nastane zaradi gibanja vlaken pod raklom pred-deaglomeracija. Delci se zatem nahajajo v zelo ohlapnem stanju in se nagibajo ustrezno malo k skepljenju. Pri nanašanju praška iz suspenzije dosežemo pred-deaglomeracijo s premazovanjem z robom, tako da mora tudi v tem primeru plinski curek prispevati le en del energije za deaglomeracijo. Razen tega imajo preddeaglomerirani delci veliko oprijemno ploskev za curek plina kar prav tako ugodno vpliva na dispergiranje.When rubbing a dry powder into velor material, pre-deagglomeration occurs due to the movement of fibers under the canister. The particles are then in a very loose state and tend to clump slightly. When applying the powder from the slurry, pre-deagglomeration is achieved by edge coating, so that even in this case the gas jet must contribute only one part of the energy for deagglomeration. In addition, pre-agglomerated particles have a large grip surface for the gas jet, which also has a beneficial effect on dispersion.
Nosilec obstaja iz materiala, ki je v bistvu raven, na katerem so razporejena tenka vlakna. Vlakna so z enim koncem ali v sredini fiksirana na ali v nosilec, pri čemer je prosti konec oz. sta oba prosta konca usmerjena navzgor in nosilec in vlakno tvorita med seboj pretežno kot 45-90°, zlasti 60-90°. Material, ki nosi vlakna je lahko npr. papir, folija iz umetne snovi ali tkanina; pri vlaknih gre lahko za naraven ali sintetičen material, npr. za bombaž, volno, svilo, viskozo, perlon, najlon, poliakril.The carrier is made of a material that is essentially the level at which thin fibers are arranged. The fibers are fixed at one end or in the middle to or in the carrier, with the free end or. the two free ends are pointing upwards and the support and the fiber form substantially 45-90 °, in particular 60-90 °. Fiber-bearing material may be e.g. paper, plastic film or fabric; the fibers may be natural or synthetic materials, e.g. for cotton, wool, silk, viscose, pearl, nylon, polyacryl.
Vlakna imajo dolžino do npr. 3 mm, zlasti do npr. 1 mm. Le-ta ne smejo biti premočno spolstena, da lahko nanesen prašek, ki je v bistvu naložen med vlakni relativno lahko spet izpihamo. Spodnja meja dolžine vlakna je pri okoli 0,1 mm. Na splošno je treba dolžino vlaken tako izbrati, da lahko naneseni prašek v želeni količini naložimo na ploskovno enoto.The fibers have a length of up to e.g. 3 mm, especially up to e.g. 1 mm. They must not be too thick so that the powder, which is essentially loaded between the fibers, can be relatively blown out again. The lower fiber length limit is about 0.1 mm. In general, the length of the fibers should be chosen so that the applied powder can be loaded onto the unit in the desired amount.
Temu ustrezno je za relativno velike količine praška na ploskovno enoto smotern nosilni material z daljšimi vlakni, medtem ko so pri zelo majhnih količinah praška na ploskovno enoto uporabna tudi krajša vlakna ali so celo prednostna. Količina praška, ki jo lahko nanesemo na ploskovno enoto je - razen od nosilnega materiala, v glavnem odvisna od vrste (gostote) praška in njegove zgostitve. Če prašek uporabljamo inhalativno moramo paziti na to, da s premočnim stiskanjem ne poslabšamo disperzije praška v uporabljenem plinskem ali zračnem curku.Accordingly, for relatively large amounts of powder per flat unit, longer fiber fibers are appropriate, while very small amounts of powder per flat unit may also use shorter fibers or even be preferred. The amount of powder that can be applied to a planar unit is - except for the carrier material, mainly dependent on the type (density) of the powder and its density. When using the powder inhalation, care must be taken not to impair the dispersion of the powder in the gas or air jet used by excessive compression.
Število vlaken na ploskovno enoto lahko močno variira. Različni tržni nosilci so se izkazali kot dobro primerni (velurna folija, žamet, pliš). Ti produkti dajejo tudi oporne točke za primemo gostoto vlaken pri drugih nosilcih. Tudi jakost vlaken lahko izberemo znotraj širokih meja. Na splošno uporabljamo vlakna s premerom 0,002 do 0,05, zlasti 0,004 do 0,03 mm. Prave žametne nosilce lahko povežemo tudi s trdim slojem, npr. zlepimo. V poštev pride tudi podloga z vpojnim slojem.The number of fibers per unit can vary greatly. Various market carriers have proven to be a good fit (velor foil, velvet, plush). These products also provide anchor points for receiving the fiber density of other carriers. Also, fiber strength can be selected within wide limits. We generally use fibers with a diameter of 0.002 to 0.05, in particular 0.004 to 0.03 mm. Real velvet beams can also be bonded to a hard layer, e.g. we stick. An absorbent liner is also suitable.
Nosilec je lahko temu ustrezno upogljiv ali tog in npr. pravokoten ali krogast. Prednostno ima nosilec obliko traku. Le-tega lahko obložimo s praškom na njegovi celotni ploskvi ali na posameznih delnih ploskvah. V zadnjem primeru lahko poteka oblaganje traku s šablono na posameznih majhnih ploskvah, npr. v obliki krogastih ploskev s premerom nekaj milimetrov, ki imajo razločno razdaljo med seboj, tako da pri izpihovanju praška iz ene od teh ploskev, prašek na sosednjih ploskvah ostane nedotaknjen.The carrier may be flexible or rigid accordingly, e.g. rectangular or circular. Preferably, the carrier has a ribbon shape. It can be coated with the powder on its entire surface or on individual partial surfaces. In the latter case, the lining of the template strip may be carried out on individual small surfaces, e.g. in the form of circular surfaces of several millimeters in diameter, having a clear distance from each other so that, when blowing the powder from one of these surfaces, the powder remains intact on the adjacent surfaces.
S količino praška na vsaki od majhnih obloženih ploskev lahko torej točno določimo dozo.With the amount of powder on each of the small coated surfaces, therefore, the dose can be accurately determined.
Če je celotna ploskev nosilca preslojena s praškom, lahko količino, ki je vsakokrat izpihana, enostavno določimo z velikostjo ploskve, ki je pri vsakem posameznem postopku odvzetja izpostavljena plinskemu curku in kije lahko npr. omejena z masko.If the entire surface of the carrier is coated with a powder, the amount that is each blown can be easily determined by the size of the surface exposed to the gas jet during each individual extraction process, which may e.g. limited by mask.
Potrebna pa maska ni. Pokazalo se je namreč, da je količina praška, ki jo izpihamo s plinskim curkom iz enakomerno obloženega nosilca, pretežno konstantna. Zato lahko dispergirano količino praška uravnamo tudi z jakostjo plinskega curka in geometrijo šob.But no mask is needed. Indeed, it has been shown that the amount of powder blown out by a gas jet from a uniformly coated carrier is substantially constant. Therefore, the dispersed amount of powder can also be controlled by the gas jet strength and nozzle geometry.
Za zaščito praškastega sloja je lahko smotrno, da nosilec npr. pokrijemo s folijo iz umetne snovi oz. tako kaširamo, da je vsakokrat odkrit samo tisti del nosilca iz katerega naj odstranimo prašek. Zlasti pri praških občutljivih na vlago pride v poštev tudi obojestransko kaširanje z aluminijem. Končno lahko uporabimo tudi nosilce, npr. trakove, pri katerih se menjujejo z vlakni zasedena področja in gladka področja.In order to protect the powder layer, it may be advantageous that the carrier e.g. cover with plastic wrap or foil. so that only the part of the carrier from which the powder is to be removed is detected. Particularly for moisture sensitive powders, both sides are coated with aluminum. Finally, carriers can be used, e.g. bands where fibers are occupied and areas smooth.
Za oblaganje nosilca najprej nanesemo po možnosti enakomerno 1-2 mm visok sloj praška (pri visoko učinkovitih zdravilnih praških in tudi pri nosilcih z zelo kratkimi vlakni je lahko sloj tudi znatno tanjši). Prašek stisnemo z raklom v trak in prebitni prašek potegnemo stran. Ta postopek po želji ponovimo enkrat ali večkrat pri čemer rakel postopoma naravnamo globje. Z gibanjem vlaken pod tlakom rakla poteka deaglomeracija skepljenih delov praška.For coating the carrier, preferably a uniformly 1-2 mm high layer of powder is first applied (for highly effective healing powders and even for carriers with very short fibers, the layer may also be significantly thinner). The powder is squeezed with a raccoon into a strip and the excess powder is pulled away. Repeat this process as desired once or more, gradually adjusting the squeegee deeper. The movement of fibers under pressure from the raccoon deagglomerates the assembled parts of the powder.
Če moramo obložiti samo določena mesta nosilca lahko nosilec pokrijemo npr. s šablono, npr. ustrezno preluknjano folijo. Če sedaj nanašamo prašek kot je zgoraj opisano, poteka odlaganje samo na tistih mestih na katerih se nahajajo luknje.If we need to cover only certain places of the carrier, the carrier can be covered e.g. with a template, e.g. properly punctured foil. If we now apply the powder as described above, only the places where the holes are located should be deposited.
Prašek lahko nanesemo na nosilec tudi v obliki suspenzije. Pri zdravilih za inhalacijo je doza učinkovine praviloma tako majhna, da zadostuje količina učinkovine, ki jo vsebuje ena kaplja suspenzije. Nato vnesemo vsakokrat eno kapljo suspenzije v želenem razmiku od naslednje kaplje. Razmike izberemo tako, da je madež praška, ki ostane po uparjenju suspenzijskega sredstva, razločno omejen od sosednjega madeža. Cilj je, da pri prevedbi praškaste učinkovine v toku dihalnega zraka, vsakokrat ločimo od nosilca samo točno tisto količino praška, ki jo nanesemo z eno kapljo.The powder can also be applied to the carrier in the form of a suspension. For inhalation medicines, the dose of the active substance is generally so small that the amount of the active substance contained in one drop of suspension is sufficient. Each drop of suspension is then introduced at the desired distance from the next drop. The intervals are chosen so that the stain of the powder remaining after evaporation of the suspension medium is clearly limited from the adjacent stain. The aim is to always separate from the carrier only the exact amount of powder that is applied in a single drop when transferring the powder into the airflow.
Oblaganje nosilca s točno dozirano količino praška na majhni ploskvi posebno dobro izpeljemo s suspenzijo.Coating the carrier with the exact dosage of powder on a small surface is particularly well done with the suspension.
Kot suspenzijsko sredstvo služijo tekoče organske spojine v katerih je prašek, ki ga je treba nanesti težko topljiv in ki se dajo po možnosti dobro odstraniti.Liquid organic compounds are used as the suspending agent, in which the powder to be applied is difficult to solubilize and which can be easily removed.
Taka suspenzijska sredstva, ki so izbrana v odvisnosti od topnostnih lastnosti snovi, oz. zmesi snovi, ki jih je treba suspendirati, so npr. diklormetan, ocetni ester, 1,1,1trikloretan ali bencin (npr. frakcija 60/95 ali 80/110). Praviloma dodamo suspenziji pomožne snovi za suspendiranje, npr. lecitin. Vsebnost trdne snovi v suspenziji znaša največ med 3 in 30 mas.%, prednostno 5 do 25 mas.%; količina pomožnih snovi za suspendiranje se giblje med npr. 0,5 in 3 mas.% z ozirom na trdno snov.Such suspending agents are selected depending on the solubility of the substance, or mixtures of substances to be suspended are e.g. dichloromethane, acetic ester, 1,1,1 trichloroethane or gasoline (eg fraction 60/95 or 80/110). As a rule, an auxiliary suspending agent is added to the suspension, e.g. lecithin. The solids content of the suspension is no more than 3 to 30% by weight, preferably 5 to 25% by weight; the amount of excipients for suspension ranges between e.g. 0.5 and 3% by weight, based on the solid.
Nosilec in suspenzija morata biti takšna, da delček praška ostane na mestu, kjer kaplja vdre v nosilec, medtem ko se suspenzijsko sredstvo nadalje porazdeli in nato upari. Uparjenje lahko pospešimo z znižanjem tlaka in/ali toploto.The carrier and the suspension must be such that the powder particle remains at the point where the droplet invades the carrier while the suspension medium is further distributed and then evaporated. Evaporation can be accelerated by reducing pressure and / or heat.
Material iz posušene suspenzijske kaplje se na splošno ne da takoj sprostiti z zračnim sunkom in dispergirati. Če pa vlakna nosilca premaknemo npr. z gladenjem z robom, se vezi praškastega delca spet prekinejo in prašek se aktivira. Posamezne delce, ki so po aktiviranju vezani s samo majhnimi veznimi silami drug na drugega ali na vlakna nosilca, lahko nato sprostimo z zračnim sunkom in dispergiramo v visokem deležu po pljučih.Generally, the material from the dried suspension droplet cannot be released immediately by air-shock and dispersed. However, if we move the carrier fibers, e.g. by smoothing with the edge, the bonds of the powder particle are broken again and the powder activated. Individual particles which, after activation, are bound by only a small binding force to each other or to the fibers of the carrier can then be released by an air shock and dispersed in high proportion by the lungs.
Namesto da sprostimo zrahljan prašek z zračnim curkom iz nosilca ga lahko zrahljamo tudi neposredno pred oz. med tem ko vodimo mimo tok dihalnega zraka na nosilcu, z drgnjenjem z robom ali z izkrtačenjem in prevedemo v zrak za vdihavanje.Instead of releasing a loose powder with an air jet from the carrier, it can also be loosened immediately before or. while passing a stream of breathing air on a carrier, by rubbing it with the edge or by twisting it and translating it into the air for inhalation.
Nanos suspenzijske kaplje ima napram nanosu suhega praška razen visoke dozirne natančnosti še to prednost, da je prašek zaradi nastanka skoije najprej zaščiten proti sproščanju zaradi pospeševanj (udarec, vibracije). Aktiviranje z drgnjenjem na robu moramo povzročiti šele tik pred sproščanjem za inhalacijo.The application of the suspension droplet, in addition to the application of the dry powder, in addition to the high dosing accuracy, has the advantage that the powder is first protected against release by accelerations (shock, vibration) due to the formation of skye. Activation by rubbing at the edge should only be induced immediately before release for inhalation.
Aparatura za nanašanje suspenzijskih kapelj v smislu izuma je shematsko predstavljena na sl. 1. Suspenzija 1 se najprej nahaja v posodi 2 za zalogo. Od tam teče skozi vod 3 k magnetnemu ventilu 4 in mimo ploskev ventila skozi vod 5 v posodo 6 z zalogo. Bat 7 zapira v legi mirovanja vstopno odprtino voda 8, iz katerega nanesemo suspenzijo na nosilec 11. Stransko lahko teče suspenzija mimo bata od voda 3 k vodu 5. Če bat z elektromagnetom potegnemo nazaj nam da prosto odprtino, tako da suspenzija lahko pride na nosilec 11. Suspenzijo iz posode 6 črpamo s črpalko 9 v posodo 2 za zalogo. Da ima suspenzija v posodi 2 za zalogo zmeraj enak nivo se nahaja med tema obema posodoma z zalogo zvezni vod 10 skozi katerega lahko teče suspenzija iz posode 2 za zalogo v posodo 6 za zalogo, če gladina tekočine prestopi vstopno odprtino tega zveznega voda. Prečni prerez vodov 3 in 10 je izbran tako majhen, da je volumski tok suspenzije, ki odteka skozi oba voda manjši, kot tok volumna katerega poganja Črpalka 9. V posodah 2 in 6 za zalogo se nahajata mešali, ki delce stalno držita v suspenziji. Za enakomerno doziranje krmilimo magnetni ventil 4 z elektronskim vodilom.The apparatus for applying the suspension droplets of the invention is schematically shown in FIG. 1. Suspension 1 is first located in container 2 for stock. From there, it flows through conduit 3 to solenoid valve 4 and past valve surfaces through conduit 5 to container 6 with stock. The piston 7 closes the inlet port 8 in the resting position, from which the suspension is applied to the carrier 11. The suspension can flow laterally from the piston from the platoon 3 to the platoon 5. If the electromagnet is pulled back, it gives us a free opening so that the suspension can reach the carrier. 11. Pump the slurry from tank 6 with pump 9 into the container 2 for storage. That the suspension in the supply container 2 is always at the same level is between these two supply tanks, a continuous line 10 through which the suspension from the supply container 2 into the supply container 6 can flow if the fluid level crosses the inlet of that continuous line. The cross-section of lines 3 and 10 is chosen so small that the volume flow of the suspension flowing through both lines is smaller than the volume flow driven by Pump 9. There are mixers in the storage tanks 2 and 6, which permanently hold the particles in suspension. For uniform dosing, control the solenoid valve 4 with an electronic guide.
Podrobnosti ventila so predstavljene na sl. 2.Valve details are presented in FIG. 2.
Primer za nanašanje zdravila kot suspenzije:Example for applying the drug as a suspension:
Suspenzijo mikroniziranega Fenoterola (delež Fenoterola: (10 mas.%) v diklormetanu ob dodatku (0,1 mas.%) lecitina nanesemo na žamet z dolžino vlakna 1,2 mm preko osnovne tkanine, po kapljicah v razmiku okoli 10 mm in posušimo. Prašek nato aktiviramo z drgnjenem z robom in izpihamo z rahlim tlakom zračnega sunka iz nosilca.A suspension of micronised Phenoterol (proportion of Phenoterol: (10% by weight) in dichloromethane, with the addition (0.1% by weight) of lecithin was applied to velvet with a fiber length of 1.2 mm over the base fabric, dropwise at intervals of about 10 mm and dried. The powder is then activated by rubbing it with the edge and blowing out with a slight pressure of air gust from the carrier.
Inhalirajoči delež iznesenih delcev (premer delca < 5,8 μτη) je 41,4 % iznesene doze.The inhalable fraction of particulate matter (particle diameter <5.8 μτη) is 41.4% of the dose delivered.
Za dispergiranje (izpih) praška zadostuje relativno majhna količina plina, npr. 10 cm3 zraka, ki jo stisnemo skozi šobo s premerom 0,5 mm.For dispersing (blowing) the powder, a relatively small amount of gas is sufficient, e.g. 10 cm 3 of air that is compressed through a nozzle 0.5 mm in diameter.
Plinski curek potreben za dispergiranje lahko proizvedemo na različne načine, npr. s cilindrom opremljenim s šobo iz katerega iztisnemo zrak z batom, ki ga poganja vzmet ali z običajnim majhnim CO2-vsebnikom, ki ga uporabljamo za tvorbo tlaka. Namesto cilindra z batom lahko uporabimo tudi naguban meh.The gas jet required for dispersion can be produced in various ways, e.g. with a cylinder fitted with a nozzle from which air is extracted by a piston driven by a spring or by a conventional small CO 2 reservoir used to generate pressure. A plunger bellows can also be used instead of a piston cylinder.
Enostavna priprava v kateri lahko uporabimo v smislu izuma obložen nosilec je shematsko predstavljena na sl. 3 in 4. Glavna sestavna dela sta dva tulca od katerih eden odvzema obložen, drugi pa izrabljen trak. Trak vodimo preko plošče (miza), pri čemer ga vodimo mimo robu za aktiviranje praška. Tukaj zadene plinski oz. zračni curek na trak in potegne prašek s seboj. Curek se na splošno sprosti v trenutku, ko dihalni zrak teče skozi ustnik. Smotrno je, da plinski oz. zračni curek sprostimo z dihalnim zrakom, da s tem koordiniramo dispergiranje praška s potekom inhalacije.A simple device in which a coated carrier can be used according to the invention is schematically illustrated in FIG. 3 and 4. The main components are two sleeves, one of which is stripped lined and the other is worn tape. The tape is guided across the board (table), leading past the edge to activate the powder. This is where gas or gas hits. air jet to the strap and pull the powder with it. The jet is generally released at the moment when the breathing air flows through the mouthpiece. It is advisable that gas or. The air jet is released with breathing air to coordinate the dispersion of the powder with the course of inhalation.
Na sl. 3 je predstavljena inhalacijska priprava od spredaj. Nosilni trak 12 s praškom, ki je v posameznih madežih v pravilnem razmiku nanesen na trak, odvijemo s tulca 13 in po izpraznjenju navijemo na tulec 14. S transportnim mehanizmom, konstruiranim na običajni način, trak vsakokrat pri delovanju priprave za toliko navijemo dalje, da pride nov madež na mizo 15. Miza 15, se nahaja v ustniku 16, skozi katerega pacient vdihava. Reža skozi katero nosilni trak 12 vodimo v ustnik je nekoliko ožja kot je debelina nosilnega traku 12. Pri tem je zgornja meja reže izdelana kot rob za aktiviranje praška. Iz cilindra 17, v katerem se nahaja pod tlakom vzmeti stoječ bat z ročajem 18, poganjamo skozi šobo zrak na madež praška. Vzmet, ki pritiska bat v smeri na mizo 15, napnemo s potegom na ročaju 18. S pripravo 19 za aretiranje, ki jo lahko sprostimo s pritiskom na gumb 20 pripravimo stopnjo dispergiranja. Med vdihavajem skozi ustnik 16 pritisne pacient na gumb 20 in s tem doseže, da bat požene količino zraka, ki je vsebovana v cilindru, skozi šobo na madež praška, tako da se prašek v dihalnem zraku dispergira.In FIG. 3 shows a frontal inhalation device. The carrier strip 12 with powder, which is applied to the strip at regular intervals at individual intervals, is unscrewed from the sleeve 13 and, after emptying, wound onto the sleeve 14. With the conveyor mechanism constructed in the usual way, the strap is rewound every time during operation of the device so that a new stain comes on table 15. Table 15 is located in the mouthpiece 16 through which the patient inhales. The slot through which the carrier strip 12 is guided into the mouthpiece is slightly narrower than the thickness of the carrier strip 12. The upper border of the slot is made as an edge for activating the powder. From the cylinder 17, in which a standing piston with a handle 18 is pressurized, a spring is driven through the nozzle to the powder stain. The spring that pushes the piston in the direction of the table 15 is tensioned by pulling on the handle 18. With the arresting device 19, which can be released by pressing the button 20, the dispersion rate is prepared. During inhalation through the mouthpiece 16, the patient presses a button 20, thereby achieving that the plunger enters the amount of air contained in the cylinder through the nozzle onto the powder stain, so that the powder is dispersed in the breathing air.
Sl. 4 shematsko prikazuje pripravo od strani, pri čemer vidimo ustnik 16 v prerezu. Šoba 21 vodi zračni tok iz cilindra 17 na madež praška.FIG. 4 schematically shows the preparation from the side, with the mouthpiece 16 in cross section. Nozzle 21 directs the air flow from the cylinder 17 to the powder stain.
Tulca z nosilcem sta tukaj v kaseti, podobni tistim, ki so običajno v kasetnih magnetofonih. Njun transport koristno zvežemo s premikanjem ročaja 18 in sicer na tak način, da pri vsakem napenjanju bata nosilni trak tako premaknemo dalje, da pride naslednji madež na mizo 15.The carrier sleeves here are in cassette, similar to those commonly found in cassette recorders. The transport is advantageously coupled by moving the handle 18 in such a way that, with each tensioning of the piston, the conveyor belt is moved so that the next stain comes to the table 15.
Namesto cilindra z vzmetjo lahko - kot omenjeno - npr. za proizvajanje plinskega curka uporabimo tudi naguban meh ali CO2-patrono običajne vrste, ki pri vsaki uporabi priprave odda nekoliko cm3 CO2. CO2 nato prav tako vodimo skozi šobo na ploskev nosilca, kije preslojena s praškom. Volumen plina, potreben za dispergiranje količine praška, ki je potrebna za terapevtske namene, znaša praviloma 3-20 cm3 (pri normalnih pogojih).Instead of a cylinder with a spring, you can - as mentioned - e.g. To produce a gas jet, we also use a pleated bellows or a CO 2 cartridge of a conventional type, which emits a little cm 3 CO 2 with each use of the device. The CO 2 is then also led through a nozzle to the surface of the powder coated carrier. The volume of gas required to disperse the amount of powder required for therapeutic purposes is generally 3-20 cm 3 (under normal conditions).
Glede na vrsto nosilca uporabimo šobe s primemo oblikovanim ustjem. V primeru okroglih madežev praška ima šoba majhno, prednostno okroglo ustje. Pri večjih ploskvah nosilca preslojenim s praškom je v danem primeru ugodnejša šoba v obliki reže ali pravokotna šoba. V tem primeru uporabimo, če je potrebno, večjo količino plina, da zagotovimo potrebno hitrost iztekanja.Depending on the type of carrier, nozzles with a primed shaped mouth are used. In the case of round powder spots, the nozzle has a small, preferably round, mouth. In the case of larger surfaces of the powder coated carrier, a slot or rectangular nozzle is preferred. In this case, a larger amount of gas is used, if necessary, to provide the required flow rate.
Pri eni vrsti poskusa določimo natančnost doziranja pri čemer bodisi (poskus 1, 2, 3) nosilni trak kontinuirno obložimo z nanašanjem suhega praška in vsakokrat preiščeno ostro omejen kos traku ali uporabimo trak pri katerem samo določena mesta obložimo s praškom.In one type of experiment, the dosage accuracy is determined whereby either (Experiments 1, 2, 3) the carrier tape is continuously coated by applying a dry powder and the sharply restricted piece of tape is searched each time, or a tape is used in which only certain places are coated with powder.
Določimo naslednje ploskovne obložitve in relativne standardne odklone:Define the following surface coatings and relative standard deviations:
* Pri nanašanju praška nosilec pokrijemo s preluknjano folijo. Luknje imajo premer 4 mm in medsebojni razmik 10-15 mm. Z izboljšanjem oblaganja lahko v nadaljnjih poskusili standardne odklone še znižamo.* When applying powder, cover the carrier with punctured foil. The holes are 4 mm in diameter and 10-15 mm apart. By improving the coating, we can further reduce the standard deviations in further attempts.
Za praktično popolno dispergiranje pri izpihovanju praška zadostuje relativno majhna količina plina, npr. 10 cm3 zraka, ki jo stisnemo skozi šobo premera 0,8 mm (v primeru madežev praška po poskusu 4). Pri tem ugotovimo odlično deaglomeracijo.For virtually complete dispersion, a relatively small amount of gas, e.g. 10 cm 3 of air compressed through a 0.8 mm diameter nozzle (in the case of powder stains after Experiment 4). This results in excellent deagglomeration.
Kot določeno z Andersenovim impaktorjem ob uporabi mikroniziranega Fenoterola je 40 % delcev iznesene doze v območju velikosti delcev pod 5,8 μτη.As determined by the Andersen impactor using micronized Phenoterol, 40% of the particulate dose is within the particle size range below 5.8 μτη.
Claims (13)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4020571A DE4020571A1 (en) | 1990-06-28 | 1990-06-28 | Device for dosing small quantities of powder esp. for asthma - powder is held between fibres of velvet-like material and is delivered, e.g. as medication into patients inhaled breath, by jet of air |
| DE19914102793 DE4102793A1 (en) | 1991-01-31 | 1991-01-31 | Medication powder-dosing carrier |
| YU111091A YU48708B (en) | 1990-06-28 | 1991-06-25 | Carrier covered with powder pharrmaceutic preparation, preparation the carrier and process for inhalation powder dosage |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SI9111110A true SI9111110A (en) | 1997-02-28 |
| SI9111110B SI9111110B (en) | 1999-06-30 |
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| SI9111110A SI9111110B (en) | 1990-06-28 | 1991-06-25 | Process and device for dosing powders |
Country Status (24)
| Country | Link |
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| EP (1) | EP0536232B1 (en) |
| JP (1) | JP3307389B2 (en) |
| KR (1) | KR0179375B1 (en) |
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| AU (1) | AU661274B2 (en) |
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| CZ (1) | CZ283510B6 (en) |
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| GR (1) | GR3017782T3 (en) |
| HU (1) | HU216129B (en) |
| IE (1) | IE69035B1 (en) |
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| NO (1) | NO304295B1 (en) |
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| RU (1) | RU2068274C1 (en) |
| SI (1) | SI9111110B (en) |
| UA (1) | UA27765C2 (en) |
| WO (1) | WO1992000115A1 (en) |
| YU (1) | YU48708B (en) |
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|---|---|---|---|---|
| US6048857A (en) * | 1989-10-17 | 2000-04-11 | Ellinwood, Jr.; Everett H. | Dosing method of administering medicaments via inhalation administration |
| DE4142238A1 (en) * | 1991-12-20 | 1993-06-24 | Boehringer Ingelheim Kg | POWDER INHALATOR WITH POWDER SUPPORT FROM REGULAR MICROSTRUCTURES |
| SE9203570D0 (en) * | 1992-11-27 | 1992-11-27 | Astra Ab | INHALES FOR MULTIPLE USE |
| US5388572A (en) * | 1993-10-26 | 1995-02-14 | Tenax Corporation (A Connecticut Corp.) | Dry powder medicament inhalator having an inhalation-activated piston to aerosolize dose and deliver same |
| US5388573A (en) * | 1993-12-02 | 1995-02-14 | Tenax Corporation | Dry powder inhalator medicament carrier |
| NZ296010A (en) * | 1994-10-21 | 1998-10-28 | Glaxo Wellcome Inc | Medicament carrier with at least one carrier screen portion for a dry powder inhalator |
| US5647347A (en) * | 1994-10-21 | 1997-07-15 | Glaxo Wellcome Inc. | Medicament carrier for dry powder inhalator |
| US5503869A (en) * | 1994-10-21 | 1996-04-02 | Glaxo Wellcome Inc. | Process for forming medicament carrier for dry powder inhalator |
| GB9610821D0 (en) * | 1996-05-23 | 1996-07-31 | Glaxo Wellcome Inc | Metering apparatus |
| US5871010A (en) * | 1996-06-10 | 1999-02-16 | Sarnoff Corporation | Inhaler apparatus with modified surfaces for enhanced release of dry powders |
| GB9616047D0 (en) | 1996-07-31 | 1996-09-11 | Glaxo Group Ltd | Medicament carrier with agglomerated large medicament particles and related method of manufacture thereof |
| GB2380472A (en) * | 2000-06-05 | 2003-04-09 | Nordson Corp | Apparatus and methods for dispensing minute amounts of liquid |
| WO2007088425A2 (en) * | 2005-12-22 | 2007-08-09 | Philip Morris Products S.A. | Inhaler device |
| CN108814979B (en) * | 2018-04-17 | 2020-09-22 | 吉林省中医药科学院 | A solid medicine feed ware for paediatrics |
| CN113650947B (en) * | 2021-08-24 | 2022-10-18 | 王霞 | Accurate medicine bottle of getting of traditional chinese medicine dripping pill |
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| DE2837040C2 (en) * | 1978-08-24 | 1982-10-21 | Siemens AG, 1000 Berlin und 8000 München | Liquid transport system for an inhalation device |
| WO1990013327A1 (en) * | 1989-04-28 | 1990-11-15 | Riker Laboratories, Inc. | Dry powder inhalation device |
| GB8909891D0 (en) * | 1989-04-28 | 1989-06-14 | Riker Laboratories Inc | Device |
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1991
- 1991-06-21 CA CA002086123A patent/CA2086123C/en not_active Expired - Fee Related
- 1991-06-21 AT AT91912093T patent/ATE127353T1/en not_active IP Right Cessation
- 1991-06-21 WO PCT/EP1991/001153 patent/WO1992000115A1/en active IP Right Grant
- 1991-06-21 DE DE59106431T patent/DE59106431D1/en not_active Expired - Fee Related
- 1991-06-21 RU RU9192016622A patent/RU2068274C1/en active
- 1991-06-21 DK DK91912093.1T patent/DK0536232T3/en active
- 1991-06-21 PL PL91297377A patent/PL165973B1/en not_active IP Right Cessation
- 1991-06-21 ES ES91912093T patent/ES2078530T3/en not_active Expired - Lifetime
- 1991-06-21 HU HUP9204100A patent/HU216129B/en not_active IP Right Cessation
- 1991-06-21 EP EP91912093A patent/EP0536232B1/en not_active Expired - Lifetime
- 1991-06-21 CZ CS923861A patent/CZ283510B6/en not_active IP Right Cessation
- 1991-06-21 KR KR1019920703384A patent/KR0179375B1/en not_active IP Right Cessation
- 1991-06-21 UA UA93003996A patent/UA27765C2/en unknown
- 1991-06-21 JP JP51106091A patent/JP3307389B2/en not_active Expired - Fee Related
- 1991-06-21 AU AU80638/91A patent/AU661274B2/en not_active Ceased
- 1991-06-25 YU YU111091A patent/YU48708B/en unknown
- 1991-06-25 SI SI9111110A patent/SI9111110B/en not_active IP Right Cessation
- 1991-06-27 PT PT98112A patent/PT98112B/en not_active IP Right Cessation
- 1991-06-27 IE IE224591A patent/IE69035B1/en not_active IP Right Cessation
- 1991-06-27 IL IL98637A patent/IL98637A/en not_active IP Right Cessation
- 1991-06-28 NZ NZ238783A patent/NZ238783A/en unknown
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1992
- 1992-12-23 NO NO925010A patent/NO304295B1/en not_active IP Right Cessation
- 1992-12-28 FI FI925882A patent/FI104410B/en active
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1995
- 1995-10-18 GR GR950402884T patent/GR3017782T3/en unknown
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