NO325134B1 - "Canisters for fuel-driven dosing aerosols" - Google Patents
"Canisters for fuel-driven dosing aerosols" Download PDFInfo
- Publication number
- NO325134B1 NO325134B1 NO20015718A NO20015718A NO325134B1 NO 325134 B1 NO325134 B1 NO 325134B1 NO 20015718 A NO20015718 A NO 20015718A NO 20015718 A NO20015718 A NO 20015718A NO 325134 B1 NO325134 B1 NO 325134B1
- Authority
- NO
- Norway
- Prior art keywords
- container
- valve
- canister
- canisters
- mixture
- Prior art date
Links
- 239000000443 aerosol Substances 0.000 title description 5
- 239000000446 fuel Substances 0.000 title 1
- 239000000203 mixture Substances 0.000 claims description 35
- 238000007789 sealing Methods 0.000 claims description 32
- 229910045601 alloy Inorganic materials 0.000 claims description 22
- 239000000956 alloy Substances 0.000 claims description 22
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 20
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 20
- 239000013543 active substance Substances 0.000 claims description 18
- 239000003380 propellant Substances 0.000 claims description 17
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 12
- 229910052782 aluminium Inorganic materials 0.000 claims description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 11
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 claims description 10
- 239000011651 chromium Substances 0.000 claims description 10
- 229910052750 molybdenum Inorganic materials 0.000 claims description 10
- 239000011733 molybdenum Substances 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 239000010949 copper Substances 0.000 claims description 9
- 229910052742 iron Inorganic materials 0.000 claims description 9
- 229910052759 nickel Inorganic materials 0.000 claims description 9
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 229910052804 chromium Inorganic materials 0.000 claims description 8
- 239000011572 manganese Substances 0.000 claims description 8
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 7
- 229910052802 copper Inorganic materials 0.000 claims description 7
- -1 hydroxide ions Chemical class 0.000 claims description 7
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims description 6
- 239000003792 electrolyte Substances 0.000 claims description 6
- 229910052748 manganese Inorganic materials 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 claims description 5
- 229910052710 silicon Inorganic materials 0.000 claims description 5
- 239000010703 silicon Substances 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 229910000831 Steel Inorganic materials 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- 150000001993 dienes Chemical class 0.000 claims description 4
- 239000010935 stainless steel Substances 0.000 claims description 4
- 229910001220 stainless steel Inorganic materials 0.000 claims description 4
- 239000010959 steel Substances 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 229920001897 terpolymer Polymers 0.000 claims description 4
- LERNTVKEWCAPOY-VOGVJGKGSA-N C[N+]1(C)[C@H]2C[C@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)C(O)(c1cccs1)c1cccs1 Chemical compound C[N+]1(C)[C@H]2C[C@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)C(O)(c1cccs1)c1cccs1 LERNTVKEWCAPOY-VOGVJGKGSA-N 0.000 claims description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 3
- OEXHQOGQTVQTAT-BZQJJPTISA-N [(1s,5r)-8-methyl-8-propan-2-yl-8-azoniabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate Chemical compound C([C@H]1CC[C@@H](C2)[N+]1(C)C(C)C)C2OC(=O)C(CO)C1=CC=CC=C1 OEXHQOGQTVQTAT-BZQJJPTISA-N 0.000 claims description 3
- 229960001609 oxitropium bromide Drugs 0.000 claims description 3
- LCELQERNWLBPSY-KHSTUMNDSA-M oxitropium bromide Chemical compound [Br-].C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)CC)=CC=CC=C1 LCELQERNWLBPSY-KHSTUMNDSA-M 0.000 claims description 3
- 229910052698 phosphorus Inorganic materials 0.000 claims description 3
- 239000011574 phosphorus Substances 0.000 claims description 3
- 239000004033 plastic Substances 0.000 claims description 3
- 229920003023 plastic Polymers 0.000 claims description 3
- 229960000257 tiotropium bromide Drugs 0.000 claims description 3
- LSLYOANBFKQKPT-DIFFPNOSSA-N 5-[(1r)-1-hydroxy-2-[[(2r)-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]benzene-1,3-diol Chemical compound C([C@@H](C)NC[C@H](O)C=1C=C(O)C=C(O)C=1)C1=CC=C(O)C=C1 LSLYOANBFKQKPT-DIFFPNOSSA-N 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 2
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 claims description 2
- 229960001022 fenoterol Drugs 0.000 claims description 2
- 229940100563 gas for inhalation Drugs 0.000 claims description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 229960002052 salbutamol Drugs 0.000 claims description 2
- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 claims description 2
- 239000006184 cosolvent Substances 0.000 claims 1
- HQQADJVZYDDRJT-UHFFFAOYSA-N ethene;prop-1-ene Chemical group C=C.CC=C HQQADJVZYDDRJT-UHFFFAOYSA-N 0.000 claims 1
- 239000004615 ingredient Substances 0.000 claims 1
- 239000000463 material Substances 0.000 description 13
- 239000007788 liquid Substances 0.000 description 9
- 238000005260 corrosion Methods 0.000 description 6
- 230000007797 corrosion Effects 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 4
- 239000005977 Ethylene Substances 0.000 description 4
- 239000004743 Polypropylene Substances 0.000 description 4
- 229920001155 polypropylene Polymers 0.000 description 4
- 230000002787 reinforcement Effects 0.000 description 4
- YFMFNYKEUDLDTL-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)C(F)(F)F YFMFNYKEUDLDTL-UHFFFAOYSA-N 0.000 description 3
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 229920001296 polysiloxane Polymers 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- WXGNWUVNYMJENI-UHFFFAOYSA-N 1,1,2,2-tetrafluoroethane Chemical compound FC(F)C(F)F WXGNWUVNYMJENI-UHFFFAOYSA-N 0.000 description 2
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 2
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000004411 aluminium Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 229910000599 Cr alloy Inorganic materials 0.000 description 1
- 239000004097 EU approved flavor enhancer Substances 0.000 description 1
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229920000459 Nitrile rubber Polymers 0.000 description 1
- 239000005062 Polybutadiene Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000000806 elastomer Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 229920002313 fluoropolymer Polymers 0.000 description 1
- 235000019264 food flavour enhancer Nutrition 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 229920002587 poly(1,3-butadiene) polymer Polymers 0.000 description 1
- 229920001084 poly(chloroprene) Polymers 0.000 description 1
- 229920002857 polybutadiene Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 239000003566 sealing material Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 229920001169 thermoplastic Polymers 0.000 description 1
- 239000004416 thermosoftening plastic Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
- C22C—ALLOYS
- C22C38/00—Ferrous alloys, e.g. steel alloys
- C22C38/18—Ferrous alloys, e.g. steel alloys containing chromium
- C22C38/40—Ferrous alloys, e.g. steel alloys containing chromium with nickel
- C22C38/44—Ferrous alloys, e.g. steel alloys containing chromium with nickel with molybdenum or tungsten
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
- B65D83/00—Containers or packages with special means for dispensing contents
- B65D83/14—Containers or packages with special means for dispensing contents for delivery of liquid or semi-liquid contents by internal gaseous pressure, i.e. aerosol containers comprising propellant for a product delivered by a propellant
- B65D83/38—Details of the container body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/009—Inhalators using medicine packages with incorporated spraying means, e.g. aerosol cans
-
- C—CHEMISTRY; METALLURGY
- C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
- C22C—ALLOYS
- C22C38/00—Ferrous alloys, e.g. steel alloys
- C22C38/18—Ferrous alloys, e.g. steel alloys containing chromium
- C22C38/40—Ferrous alloys, e.g. steel alloys containing chromium with nickel
- C22C38/42—Ferrous alloys, e.g. steel alloys containing chromium with nickel with copper
Landscapes
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Mechanical Engineering (AREA)
- Materials Engineering (AREA)
- Metallurgy (AREA)
- Organic Chemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- General Health & Medical Sciences (AREA)
- Pulmonology (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Dispersion Chemistry (AREA)
- Hematology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Containers And Packaging Bodies Having A Special Means To Remove Contents (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
- Preventing Corrosion Or Incrustation Of Metals (AREA)
- Filling Or Discharging Of Gas Storage Vessels (AREA)
- Safety Valves (AREA)
- Nozzles (AREA)
Description
Foreliggende oppfinnelse omhandler korrosjonsbestandige kanistere med beholdere for i rustfritt stål for drivmiddeldrevet doseringsaerosoler for bruk i drivmiddeldrevne inhalatorer. The present invention relates to corrosion-resistant canisters with stainless steel containers for propellant-powered dosing aerosols for use in propellant-powered inhalers.
Bakgrunn for oppfinnelsen Background for the invention
I drivmiddeldrevne inhalatorer, er de aktive substansene oppbevart sammen med drivmidlet i patronlignende kanistere. Disse kanistrene består generelt av en aluminiumskanister forseglet med en aluminium ventilskål i hvilken ventil er innebygget. En kanister av denne typen kan dermed bli plassert i inhalatoren i form av en patron og blir enten etterlatt der permanent eller byttet med ny patron etter bruk. Siden klorofluorkarboner (CFC) ble forbudt på bakgrunn av Rio de Janeiro konferansen på begynnelsen av 90-tallet, er bruken av fluorhydrokarboner (FHC) anbefalt som et alternativ til bruk i drivmiddeldrevne inhalatorer. Det mest lovende eksemplet til dato er TG 134a (1,1,2,2-tetrafluoroetan og TG 227 (1,1,1,2,3,3,3-heptafluoropropan). Følgelig måtte eksiterende systemer for leveranse av behandling ved inhalering konverteres til CFC-frie drivmidler og nye leveransesystemer og aktive substanser måtte bli utviklet. Overraskende ble det funnet at aluminiumskanistere ikke alltid er motstandsdyktige mot medisinblandinger bestående av fluorohydrokarboner som drivmiddel, men har en stor risiko for korrosjon avhengig av komposisjonen til blandingen. Dette er spesielt riktig for blandinger som inneholder elektrolytter og/eller frie ioner, spesielt frie halider. I disse tilfellene er aluminiumen angrepet hvilket betyr at aluminium ikke kan benyttes som rørmateriale for kanisterne. Lignende ustabilitet i aluminiumskanistere har blitt observert når fluorokarboner har vært brukt som drivmiddel dersom blandingen inneholder sure eller basiske komponenter, dvs i form av aktive substanser, tilsetningsmidlene i form av stabilisatorer, overflateaktive stoffer, smaksforsterkere, antioksidanter, etc. In propellant-powered inhalers, the active substances are stored together with the propellant in cartridge-like canisters. These canisters generally consist of an aluminum canister sealed with an aluminum valve bowl in which the valve is built-in. A canister of this type can thus be placed in the inhaler in the form of a cartridge and is either left there permanently or replaced with a new cartridge after use. Since chlorofluorocarbons (CFCs) were banned on the basis of the Rio de Janeiro conference in the early 90s, the use of fluorohydrocarbons (FHCs) has been recommended as an alternative for use in propellant-powered inhalers. The most promising examples to date are TG 134a (1,1,2,2-tetrafluoroethane) and TG 227 (1,1,1,2,3,3,3-heptafluoropropane). Consequently, exciting systems for the delivery of treatment by inhalation had to converted to CFC-free propellants and new delivery systems and active substances had to be developed. Surprisingly, it was found that aluminum canisters are not always resistant to drug mixtures consisting of fluorohydrocarbons as propellants, but have a high risk of corrosion depending on the composition of the mixture. This is particularly correct for mixtures containing electrolytes and/or free ions, especially free halides. In these cases the aluminum is attacked which means that aluminum cannot be used as a pipe material for the canisters. Similar instability in aluminum canisters has been observed when fluorocarbons have been used as propellant if the mixture contains acidic or basic components, i.e. in the form of active substances, the additives in the form of stabilizers, surfactants, flavor enhancers, antioxidants, etc.
Fra US 4 944 433 og US 5,037,012 fremgår det en ventil av rustfritt stål for en aerosolbeholder. US 5,037,012 beskriver også en ventil for en aerosolbeholder. US 4,944,433 and US 5,037,012 disclose a stainless steel valve for an aerosol container. US 5,037,012 also describes a valve for an aerosol container.
Beskrivelse av oppfinnelsen Description of the invention
En av oppgavene til foreliggende oppfinnelse er å frembringe en beholder for drivmiddeldrevne inhalatorer som er korrosjonsbestandige ved tilstedeværelse av aktive substansblandinger for behandling ved inhalering inneholdene fluor-karboner som drivmiddel, som har tilstrekkelig kompresjons- og bruddmotstand for å stå i mot prosessering og bruk, og som sikrer kvaliteten til blandingene som oppbevares i denne og overvinner andre ulemper kjent fra kjent teknikk. One of the tasks of the present invention is to produce a container for propellant-driven inhalers that is corrosion-resistant in the presence of active substance mixtures for treatment by inhalation containing fluorocarbons as propellant, which has sufficient compression and breaking resistance to withstand processing and use, and which ensures the quality of the mixtures stored therein and overcomes other disadvantages known from the prior art.
En ytterligere hensikt med oppfinnelsen er å frembringe en kanister for drivmiddeldrevne beholdere, hvilken beholder består av et enkelt iboende homogent materiale. A further purpose of the invention is to produce a canister for propellant-driven containers, which container consists of a single intrinsically homogeneous material.
Således beskriver den foreliggende oppfinnelsen en beholder inneholdende en blanding av aktive substanser som inneholder salt, syre, base eller elektrolytt med TG 134a og/eller TG 227 som drivmiddelgass for inhaleringsbehandling, idet beholderen består av et sylindrisk parti (4) og en ventilskål (8) med en ventil (9) innebygd i denne. Beholderen inneholder en legering med 40,0 - 53,0% jern, 23,0 - 28,0% nikkel, 19,0 - 23,0% krom, 4,0 - 5,0% molybden, 0,0 - 2,0% mangan, 1,0 - 2,0% kopper, 0,0 - 1,0% silisium, 0,0 -0,045% av fosfor, 0,0 - 0,035% svovel og 0,0 - 0,020% karbon. Thus, the present invention describes a container containing a mixture of active substances containing salt, acid, base or electrolyte with TG 134a and/or TG 227 as propellant gas for inhalation treatment, the container consisting of a cylindrical part (4) and a valve bowl (8 ) with a valve (9) built into it. The container contains an alloy with 40.0 - 53.0% iron, 23.0 - 28.0% nickel, 19.0 - 23.0% chromium, 4.0 - 5.0% molybdenum, 0.0 - 2 .0% manganese, 1.0 - 2.0% copper, 0.0 - 1.0% silicon, 0.0 -0.045% of phosphorus, 0.0 - 0.035% sulfur and 0.0 - 0.020% carbon.
Videre beskriver oppfinnelsen at beholderen kan ha en veggtykkelse på 0,1 til 0,5 mm, fortrinnvis 0,15 til 0,35 mm, at beholderen kan ha en veggtykkelse på 0,19 til 3,0 mm, samt en anvendelse av en beholder av denne typen for en blanding i beholderen med en pH på 2,0 til 5,0. Furthermore, the invention describes that the container can have a wall thickness of 0.1 to 0.5 mm, preferably 0.15 to 0.35 mm, that the container can have a wall thickness of 0.19 to 3.0 mm, as well as the use of a container of this type for a mixture in the container with a pH of 2.0 to 5.0.
Overraskende har det blitt funnet at beholdere bestående av en beholder og en ventilskål med ventil i denne hvor beholderen består av visse rustfrie legeringer løser dette problemet ifølge oppfinnelsen. Disse legeringene består av komponenter som krom (Cr), nikkel (Ni), molybden (Mo), jern (Fe) og karbon (C). Slike legeringer kan i tillegg inneholde kopper (Cu), mangan (Mn) og silikon (Si). Beholderen består fortrinnvis av en av legeringene beskrevet ovenfor. Surprisingly, it has been found that containers consisting of a container and a valve bowl with a valve therein, where the container is made of certain stainless alloys, solve this problem according to the invention. These alloys consist of components such as chromium (Cr), nickel (Ni), molybdenum (Mo), iron (Fe) and carbon (C). Such alloys may also contain copper (Cu), manganese (Mn) and silicon (Si). The container preferably consists of one of the alloys described above.
Oppfinnelsen omhandler videre bruken av en beholder eller kanister av denne typen bestående av en beholder og en ventilskål med ventil i drivmiddeldrevne doseringsaerosoler (inhalatorer) og en prosess for å produsere dem. The invention further relates to the use of a container or canister of this type consisting of a container and a valve cup with a valve in propellant-driven dosing aerosols (inhalers) and a process for producing them.
Oppfinnelsen er heretter beskrevet mer utførende med referanse til figur 1 og 2. The invention is hereinafter described in more detail with reference to figures 1 and 2.
Figur 1 viser kanisteren bestående av en beholder (2), en ventilskål (8) og ventilen (9) i et tverrsnitt. Figur 2 viser viser en annen utførelsesform av ventilskålen (8) og ventilen (9) i tverrsnittet. Figur 1 viser en kanister (1) ifølge oppfinnelsen i tverrsnitt. Kanisteren (1) består av en beholder (2) for oppbevaring av farmaseutisk blandinger og en ventilskål (8) med ventil (9). Formen og dimensjonene til kanisteren tilsvarer til de aluminiumskanisterne som er kjent fra kjent teknikk. Figure 1 shows the canister consisting of a container (2), a valve cup (8) and the valve (9) in a cross section. Figure 2 shows another embodiment of the valve bowl (8) and the valve (9) in cross-section. Figure 1 shows a canister (1) according to the invention in cross section. The canister (1) consists of a container (2) for storing pharmaceutical mixtures and a valve bowl (8) with valve (9). The shape and dimensions of the canister correspond to the aluminum canisters known from the prior art.
Beholderen (2) ifølge oppfinnelsen er laget av en legering bestående av 40,0 - 53,0% jern The container (2) according to the invention is made of an alloy consisting of 40.0 - 53.0% iron
23,0 - 28,0% nikkel 23.0 - 28.0% nickel
19,0-23,0% krom 19.0-23.0% chromium
4,0 - 5,0% molybden 4.0 - 5.0% molybdenum
0,0- 2,0% mangan 0.0-2.0% manganese
1,0-2,0% kopper 1.0-2.0% copper
0,0 - 1,0% silikon 0.0 - 1.0% silicone
0,0 - 0,045% fosfor 0.0 - 0.045% phosphorus
0,0 - 0,035% svovel 0.0 - 0.035% sulfur
0,0 - 0,020% karbon 0.0 - 0.020% carbon
Denne legeringen er en legering ifølge materialnummer 1.4539 i Jern og Stållisten til Foreningen til tyske metallurger. This alloy is an alloy according to material number 1.4539 in the Iron and Steel List of the Association of German Metallurgists.
En foretrukket legering av denne typen har følgende sammensetning: 19,0-21,0% krom A preferred alloy of this type has the following composition: 19.0-21.0% chromium
24,0 - 26,0% nikkel 24.0 - 26.0% nickel
4,0-5,0% molybden 4.0-5.0% molybdenum
0,0 - 2,0% kopper 0.0 - 2.0% copper
inntil 2,0% mangan up to 2.0% manganese
inntil 0,5% silikon og up to 0.5% silicone and
inntil 0,02% karbon, hvorav resten hovedsaklig er jern. up to 0.02% carbon, the rest of which is mainly iron.
I en nesten identisk alternativ legering er innholdet av molybden begrenset til 4,5 - 5,0%. In an almost identical alternative alloy, the content of molybdenum is limited to 4.5 - 5.0%.
I en alternativ utførelsesform er beholderen (2) ifølge oppfinnelsen bestående av en legering ifølge materialnummer 1.4404 i Jern og Stållisten til Foreningen til tyske metallurger. In an alternative embodiment, the container (2) according to the invention consists of an alloy according to material number 1.4404 in the Iron and Steel List of the Association of German Metallurgists.
Sammensetningen til legeringen er: The composition of the alloy is:
60,0 - 72,0% jern 60.0 - 72.0% iron
9,0-13,0% nikkel 9.0-13.0% nickel
17,0-21,0% krom 17.0-21.0% chromium
0,0 - 3,0% molybden 0.0 - 3.0% molybdenum
0,0 - 3,0% mangan 0.0 - 3.0% manganese
0,0-1,5 silikon 0.0-1.5 silicone
0,0 - 0,04% svovel og 0.0 - 0.04% sulfur and
0,0 - 0,03% karbon. 0.0 - 0.03% carbon.
En annen utførelsesform av beholderen består av en legering med følgende sammensetning: 16,5-18,5% krom Another embodiment of the container consists of an alloy with the following composition: 16.5-18.5% chromium
11,0-14,0% nikkel 11.0-14.0% nickel
0,1 -2,5% molybden 0.1 -2.5% molybdenum
maksimalt 0,03% karbon, hvorav resten består av jern. maximum 0.03% carbon, the rest of which consists of iron.
Legeringene som er nevnte ovenfor er slik at de er korrosjonsbestandige mot forskjellige flytende fluorokarboner slik som TG 134a (1,1,1,3-tetrafluoro-hydrokarbon) og TG 227 (1,1,1,2,3,3,3-heptafluoropropan). Disse inkluderer gassblandinger som drivmiddel som har aktive substanser som er egnede for behandling ved inhalering, overflatemiddel, biløsemiddel, stabilisatorer, kompleks-dannere, smaksregulatorer, antioksidanter, salter, syrer, baser eller elektrolytter slik som hydroksidioner, cyanidioner og/eller halid anioner slik som fluorid, klorid, bromid eller jodid. The alloys mentioned above are such that they are corrosion resistant to various liquid fluorocarbons such as TG 134a (1,1,1,3-tetrafluoro-hydrocarbon) and TG 227 (1,1,1,2,3,3,3- heptafluoropropane). These include gas mixtures such as propellants that have active substances suitable for treatment by inhalation, surfactants, autosolvents, stabilizers, complexing agents, flavor regulators, antioxidants, salts, acids, bases or electrolytes such as hydroxide ions, cyanide ions and/or halide anions such as fluoride, chloride, bromide or iodide.
Beholderen (2) er formet fra et rør laget fra en av de ovenfor beskrevne legeringene. Beholderen (2) har fire forskjellige soner: den flate eller konkave, innoverbøyde kuppelbase (3), et sylindrisk parti (4) hvilket går sammen med en avfaset krage (5) i den siste tredelen og ender til slutt i forsterkningsribben (6) hvilken omslutter åpningen (7) til beholderen. The container (2) is formed from a tube made from one of the alloys described above. The container (2) has four different zones: the flat or concave, inwardly bent dome base (3), a cylindrical part (4) which joins a chamfered collar (5) in the last wooden part and finally ends in the reinforcement rib (6) which encloses the opening (7) of the container.
Veggtykkelsen til beholderen (2) er mellom 0,1 og 0,5 mm i en foretrukket utførelsesform, fortrinnsvis mellom 0,15 og 0,35 mm, mest foretrukket omlag 0,19 til 3,0 mm. The wall thickness of the container (2) is between 0.1 and 0.5 mm in a preferred embodiment, preferably between 0.15 and 0.35 mm, most preferably around 0.19 to 3.0 mm.
I en foretrukket utførelsesform av beholderen (2) kan denne motstå et sprengningstrykk på mer enn 30 000 hPa, fortrinnsvis mer enn 100 000 hPa, mest foretrukket mer enn 200 000 hPa. Vekten av beholderen (5) er 5-15 g i en foretrukket utførelsesform, 7-10 g i en annen og 7,9 - 8,7 g i igjen en annen. I en like fortrukket utførelsesform av beholderen (2) har denne et volum på 10 til 20 ml mens andre har volumer rundt 15 - 18 ml. In a preferred embodiment of the container (2), this can withstand a burst pressure of more than 30,000 hPa, preferably more than 100,000 hPa, most preferably more than 200,000 hPa. The weight of the container (5) is 5-15 g in a preferred embodiment, 7-10 g in another and 7.9 - 8.7 g in yet another. In an equally preferred embodiment of the container (2), this has a volume of 10 to 20 ml, while others have volumes of around 15 - 18 ml.
I den forseglede tilstanden av beholderen (2) er denne tett forseglet ved hjelp av ventilskålen (8) etter at denne er fyllt opp med den farmaseutiske blandingen og drivmiddelet. In the sealed state of the container (2), this is tightly sealed by means of the valve cup (8) after it has been filled up with the pharmaceutical mixture and the propellant.
I en utførelsesform av ventilskålen (8) består denne av aluminium. I dette tilfellet er pakningen (10) og/eller ventilen (9) konstruert på en slik måte at ventilen (8) selv ikke kan komme i kontakt med væsken på innsiden av beholderen. In one embodiment of the valve bowl (8), this consists of aluminium. In this case, the gasket (10) and/or the valve (9) are constructed in such a way that the valve (8) itself cannot come into contact with the liquid inside the container.
I en annen utførelsesform består ventilskålen (8) av aluminium. I dette tilfellet er pakningen (10) og/eller ventilen (9) konstruert slik at ventilskålen (8) selv ikke kan komme i kontakt med væsken på innsiden av beholderen. In another embodiment, the valve bowl (8) consists of aluminium. In this case, the gasket (10) and/or the valve (9) are constructed so that the valve bowl (8) itself cannot come into contact with the liquid inside the container.
I en foretrukket utførelsesform av ventilskålen (8) som er beskrevet i GB 2324121, hvorved med dette er å betrakte som fullt beskrevet ved referanse. In a preferred embodiment of the valve bowl (8) which is described in GB 2324121, whereby this is to be considered as fully described by reference.
I den stengte tilstanden til kanisteren, er ventilskålen (8) krympet rundt beholderen (2) ved forsterkingsribben (6). I foretrukne utførelsesformer forsegler en pakning eller tetningsring ventilskålen (8) relativt til forsterkningsribben (8). Pakningen kan være ringformet eller plateformet. Den er fortrinnsvis plateformet. Den kan bestå av materialer kjent fra kjent teknikk som er egnede for å benyttes sammen med farmaseutiske blandinger med fluorohydrokarboner som drivmiddel. Eksempler på egnede materialer inkluderer termoplaster, elastomerer, materialer som neopren, isobutylen, isoprene, butadiengummi, nitrilgummi, kopolymerer av etylen og polypropylen, terpolymer av etylen, polypropylen og en dien, f eks butadiene eller fluorbehandlede polymerer. Det foretrukne materiale er etylen/- polypropylen/ dien-terpolymerer (EPDM). In the closed state of the canister, the valve cup (8) is crimped around the container (2) by the reinforcement rib (6). In preferred embodiments, a gasket or sealing ring seals the valve cup (8) relative to the reinforcement rib (8). The packing can be ring-shaped or plate-shaped. It is preferably the platform. It can consist of materials known from the prior art which are suitable for use together with pharmaceutical mixtures with fluorohydrocarbons as propellants. Examples of suitable materials include thermoplastics, elastomers, materials such as neoprene, isobutylene, isoprene, butadiene rubber, nitrile rubber, copolymers of ethylene and polypropylene, terpolymer of ethylene, polypropylene and a diene, e.g. butadiene or fluorinated polymers. The preferred material is ethylene/polypropylene/diene terpolymers (EPDM).
På den ene siden av ventilskålen (8) som vender mot innsiden til beholderen, er en ventil (9) konstruert slik at ventilstammen (12) går igjennom ventilskålen (8) til den andre siden. Ventilen (9) sitter i den midtstilte åpningen til tetningsringen (10) for å danne en pakning. Tetningsringen (10) og ventilen (9) forsegler sammen ventilskålen fra innsiden til beholderen slik at denne ikke kan komme i kontakt med væsken i beholderen (2). On one side of the valve bowl (8) facing the inside of the container, a valve (9) is constructed so that the valve stem (12) passes through the valve bowl (8) to the other side. The valve (9) sits in the center opening of the sealing ring (10) to form a seal. The sealing ring (10) and the valve (9) together seal the valve bowl from the inside of the container so that it cannot come into contact with the liquid in the container (2).
Ventilen (9) er konstruert slik at hvert element som er i stand til å komme i kontakt med væsken på innsiden til beholderen (2) består av et materiale som er korrosjonsbestandig med hensyn til denne væsken. Slike elementer inkluderer eksempelvis fjæren eller fjærene (11), ventilstammen (12), som strekker seg fra innsiden til utsiden gjennom åpningen (17) i ventilskålen (8), doseringskammeret (13) og ventilhuset (14). Fjæren (11) består av stål, fortrinnvis av legeringen som er beskrevet ovenfor og/eller et plastmateriale. Elementene (12), (13) og (14) består fortrinnsvis av en plast, spesielt en polyester, mest fortrinnsvis polybutyl-tereftalat. The valve (9) is constructed so that each element that is able to come into contact with the liquid on the inside of the container (2) consists of a material that is corrosion resistant with respect to this liquid. Such elements include, for example, the spring or springs (11), the valve stem (12), which extends from the inside to the outside through the opening (17) in the valve bowl (8), the dosing chamber (13) and the valve housing (14). The spring (11) consists of steel, preferably of the alloy described above and/or a plastic material. The elements (12), (13) and (14) preferably consist of a plastic, especially a polyester, most preferably polybutyl terephthalate.
Som vist i figur (1) kan en eller flere pakninger eller tetningsringer, dvs tetningsringene (15) og/eller (16), kan være frembrakt for å forhindre væske eller gass fra å slippe ut fra innsiden av beholderen. Tetningsringen eller tetningsringene kan være arrangert slik at væsken på innsiden av beholderen kommer i kontakt med innkledningen til beholderen og ventilen, med unntak av den faktiske tetningsringen eller tetningsringene. As shown in figure (1), one or more gaskets or sealing rings, i.e. the sealing rings (15) and/or (16), can be provided to prevent liquid or gas from escaping from inside the container. The sealing ring or sealing rings may be arranged so that the liquid inside the container comes into contact with the lining of the container and the valve, with the exception of the actual sealing ring or sealing rings.
Tetningsringen (15) forsegler ventilstammen hvilken er valgfritt vertikalt bevegelig ved det punktet hvor den trenger igjennom ventilskålen (8). Tetningsringen (16) forsegler ventilskålen (8) på innsiden til ventilen i forhold til ventilhuset og/eller doseringskammeret (13). På denne måten forhindrer tetningsringene (15) og (16) noe som helst væske eller gass fra å slippe ut fra innsiden av beholderen langs det ytre røret til ventilstammen og ut av kanisteren eller fra å komme i kontakt med ventilskålen på denne leden. Tetningsringene (15) og (16) kan være laget av det samme materialet som tetningsringen (10), fortrinnsvis et etylen/polypropylen/ dien-terpolymerer. The sealing ring (15) seals the valve stem which is optionally vertically movable at the point where it penetrates the valve bowl (8). The sealing ring (16) seals the valve cup (8) on the inside of the valve in relation to the valve housing and/or the dosing chamber (13). In this way the sealing rings (15) and (16) prevent any liquid or gas from escaping from inside the container along the outer tube of the valve stem and out of the canister or from contacting the valve cup at this joint. The sealing rings (15) and (16) can be made of the same material as the sealing ring (10), preferably an ethylene/polypropylene/diene terpolymer.
I en av utførelsesformene hvor ventilskålen (8) ikke er laget av aluminium men en av de korrosjonsbestandige materialene ovenfor, er det nødvendig for tetningsringen (10) sammen med ventilen (9) å isolere ventilskålen fullstendig fra innsiden til beholderen. Derfor er det ikke nødvendig i dette tilfellet for tetningsringen (10) og ventilen (9) å være i forseglende kontakt med hverandre. Det kan være en spalte mellom tetningsringen (10) og ventilen (9). I et slikt tilfelle sitter tetningsringen (10) direkte på undersiden av ventilskålen (8) relativt til forsterkningsribben (6) på beholderen. Tetningsringen (15) forsegler dermed åpningen (17) i ventilskålen (8) fra innsiden av beholderen. In one of the embodiments where the valve bowl (8) is not made of aluminum but one of the corrosion-resistant materials above, it is necessary for the sealing ring (10) together with the valve (9) to isolate the valve bowl completely from the inside of the container. Therefore, it is not necessary in this case for the sealing ring (10) and the valve (9) to be in sealing contact with each other. There may be a gap between the sealing ring (10) and the valve (9). In such a case, the sealing ring (10) sits directly on the underside of the valve bowl (8) relative to the reinforcement rib (6) on the container. The sealing ring (15) thus seals the opening (17) in the valve bowl (8) from the inside of the container.
Figur 2 viser en annen utførelsesform til ventilskålen (8) med en innebygget ventil (9). Denne utførelsesformen er i store trekk identisk til den i figur 1. Den største forskjellen ligger i det at tetningsringen (10) og tetningsringen (16) i ut-førelsesformen i figur 2 er kombinert for sammen å danne en tetningsring (18). Tetningsringen (18) omslutter undersiden til ventilplaten (18). Den er arrangert slik at ventilhuset (14) er innebygget i tetningsringen (18). Ventilstammen (12) strekker seg gjennom tetningsringen via åpningen (19) som er plassert direkte under åpningen (17) i ventilskålen (8). Åpningen (19) innehar slike dimensjoner for å forsegle ventilstammen (12) relativt til ventilskålen (8). Det tettende materiale for tetningsringen (18) er identisk til det for tetningsringen (10). Figure 2 shows another embodiment of the valve bowl (8) with a built-in valve (9). This embodiment is largely identical to the one in Figure 1. The biggest difference lies in the fact that the sealing ring (10) and the sealing ring (16) in the embodiment in Figure 2 are combined to form a sealing ring (18). The sealing ring (18) encloses the underside of the valve plate (18). It is arranged so that the valve housing (14) is built into the sealing ring (18). The valve stem (12) extends through the sealing ring via the opening (19) which is located directly below the opening (17) in the valve bowl (8). The opening (19) has such dimensions to seal the valve stem (12) relative to the valve cup (8). The sealing material for the sealing ring (18) is identical to that for the sealing ring (10).
Beholderen (2) ifølge oppfinnelsen er produsert analogt til prosessen som fra kjent teknikk for produksjon av aluminiumskanistere og dess like, i hvilken beholderen er utstemplet fra en tynn plate av det aktuelle materialet eller den tilsvarende legeringen. I foreliggende oppfinnelse er beholderen (2) stemplet ut fra en tynn plate av de ovenfor nevnte legeringer av krom (Cr), nikkel (Ni), molybden (Mo), jern (Fe), karbon (C) eller fra en annen legering som i tillegg inneholder kopper (Cu), mangan (Mn) og silikon (Si). The container (2) according to the invention is produced analogously to the process from known technology for the production of aluminum canisters and the like, in which the container is stamped from a thin plate of the material in question or the corresponding alloy. In the present invention, the container (2) is stamped from a thin plate of the above-mentioned alloys of chromium (Cr), nickel (Ni), molybdenum (Mo), iron (Fe), carbon (C) or from another alloy which additionally contains copper (Cu), manganese (Mn) and silicon (Si).
Kanisteren bestående av en beholder (2) og en ventilskål med ventil (8) ifølge oppfinnelsen er spesielt egnet for benyttelse av drivgassblandinger som inneholder fluorohydrokarboner. Drivgassblandinger som fortrinnsvis kan benyttes i forbindelse med oppfinnelsen er beskrevet i patentskrift WO 94/13262, til hvilken referanse herved er foretatt. Spesielt foretrukne blandinger beskrevet i dette skriftet er syrestabiliserende og/eller etanole drivgassblandinger inneholdene: 1,1,2,2-tetrafluoretan (TG 134a) og/eller 1,1,1,2,3,3,3-heptafluorpropan (TG 227) som drivgass, spesielt de som inneholder ipatropiumbromid, oksitropiumbromid, albuterol, tiotropiumbromid eller fenoterol som aktive substanser. The canister consisting of a container (2) and a valve bowl with valve (8) according to the invention is particularly suitable for the use of propellant gas mixtures containing fluorohydrocarbons. Propellant gas mixtures which can preferably be used in connection with the invention are described in patent document WO 94/13262, to which reference is hereby made. Particularly preferred mixtures described in this document are acid stabilizing and/or ethanol propellant gas mixtures containing: 1,1,2,2-tetrafluoroethane (TG 134a) and/or 1,1,1,2,3,3,3-heptafluoropropane (TG 227 ) as propellant, especially those containing ipatropium bromide, oxitropium bromide, albuterol, tiotropium bromide or fenoterol as active substances.
Avhengig av de aktive substansene kan uorganiske eller organiske syrer benyttes som stabilisatorer. Eksempler på uorganiske syrer inkluderer, i tillegg til haliske syrer og andre (halic acids mineralsyrer: svovelsyre, saltsyre, salpetersyre eller fosforsyre, men eksempler på organiske syrer inkluderer askorbinsyre eller sitronsyre. I tilfeller med salt som den aktive substansen, er de foretrukne syrene de hvorved anion er identisk til de hvor salt er den aktive substansen. Sitronsyre er generelt egnet for alle aktive substanser og deres salter og er mest foretrukket. Depending on the active substances, inorganic or organic acids can be used as stabilizers. Examples of inorganic acids include, in addition to halic acids and other (halic acids) mineral acids: sulfuric acid, hydrochloric acid, nitric acid or phosphoric acid, but examples of organic acids include ascorbic acid or citric acid. In cases with salt as the active substance, the preferred acids are those wherein the anion is identical to those where the salt is the active substance Citric acid is generally suitable for all active substances and their salts and is most preferred.
Syreinnholdet er slik at pH'en til blandingen er mellom 1.0 og 7.0, fortrinnsvis mellom 2.0 og 5.0 og mest foretrukket rundt 3.5.1 tilfellet med uorganiske syrer er syreinnholdet i området fra omlag 0.00002 til 0.01 N. I tilfeller med askorbinsyre er det foretrukne innholdet omtrentlig i området fra 0.0045 til 5.0 mg/ml og i tilfellet med sitronsyre er det i området fra 0.0039 til 27.7 mg/ml. The acid content is such that the pH of the mixture is between 1.0 and 7.0, preferably between 2.0 and 5.0 and most preferably around 3.5.1 in the case of inorganic acids the acid content is in the range from about 0.00002 to 0.01 N. In cases of ascorbic acid the preferred content is approximately in the range from 0.0045 to 5.0 mg/ml and in the case of citric acid it is in the range from 0.0039 to 27.7 mg/ml.
Blandingene kan i tillegg inneholde etanol som biløsemiddel. Den foretrukne mengden er 1.0 til 50.0% ved vekt i blandingen. The mixtures may also contain ethanol as a car solvent. The preferred amount is 1.0 to 50.0% by weight in the mixture.
I det følgende er det noen foretrukne blandinger med eksempler på det som kan oppbevares i en kanister eller i en beholder av den typen som er beskrevet ovenfor: The following are some preferred mixtures with examples of what can be stored in a canister or in a container of the type described above:
Eksempel 1 Example 1
Eksempel 2 Example 2
Eksempel 3 Example 3
Eksempel 4 Eksempel 5 Eksempel 6 Example 4 Example 5 Example 6
En fremgangsmåte for å fylle kanisteren med tilsvarende blandinger kan være, for eksempel, metoden med to-trinns trykkfylling, metoden med et-trinns kaldfylling eller den et-trinns trykkfyllingsmetoden. A method of filling the canister with corresponding mixtures can be, for example, the two-step pressure filling method, the one-step cold filling method or the one-step pressure filling method.
Claims (18)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19924098A DE19924098A1 (en) | 1999-05-26 | 1999-05-26 | Stainless steel canister for propellant-powered MDIs |
| PCT/EP2000/004662 WO2000073170A1 (en) | 1999-05-26 | 2000-05-24 | Special steel canister for propellant-operated dosing aerosols |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20015718D0 NO20015718D0 (en) | 2001-11-23 |
| NO20015718L NO20015718L (en) | 2002-01-24 |
| NO325134B1 true NO325134B1 (en) | 2008-02-04 |
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| NO20015718A NO325134B1 (en) | 1999-05-26 | 2001-11-23 | "Canisters for fuel-driven dosing aerosols" |
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1999
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| MK1K | Patent expired |