NO179996B - Sprayed preparations containing 5HT1-like receptor antagonists - Google Patents
Sprayed preparations containing 5HT1-like receptor antagonists Download PDFInfo
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- NO179996B NO179996B NO920039A NO920039A NO179996B NO 179996 B NO179996 B NO 179996B NO 920039 A NO920039 A NO 920039A NO 920039 A NO920039 A NO 920039A NO 179996 B NO179996 B NO 179996B
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- indole
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- Medicinal Preparation (AREA)
Description
Foreliggende oppfinnelse angår farmasøytiske preparater som inneholder virkestoff med selektiv agonistvirkning på 5HT^-lignende reseptorer, spesielt et preparat for peroral administrasj on. The present invention relates to pharmaceutical preparations containing an active substance with selective agonist action on 5HT 2 -like receptors, in particular a preparation for oral administration.
5HT^-lignende reseptorer forekommer for eksempel i vena saphena hos hunder, og 5HT^-lignende reseptoragonister som foreliggende oppfinnelse angår, kontraherer denne vena saphena. Slike forbindelser kan derfor identifiseres gjennom deres kontraherende virkning på strimler fra vena saphena isolert fra hund, som beskrevet for eksempel av Apperley et al., (Br. J. Pharmacol. 68, 215-224, 1980). Forbindelser som er selektive 5HT1~lignende reseptoragonister har også vist seg selektivt å kontrahere arteria carotis-sengen hos anestetiserte hunder. 5HT^-like receptors occur, for example, in the saphenous vein in dogs, and 5HT^-like receptor agonists to which the present invention relates contract this saphenous vein. Such compounds can therefore be identified by their contractile effect on strips from saphenous vein isolated from dog, as described for example by Apperley et al., (Br. J. Pharmacol. 68, 215-224, 1980). Compounds that are selective 5HT1~-like receptor agonists have also been shown to selectively contract the carotid artery bed in anesthetized dogs.
En rekke forbindelser som selektivt kontraherer strimler av vena saphena isolert fra hund og som kontraherer arteria carotis-sengen i anestetiserte hunder, er tidligere beskrevet. Forbindelsene innbefatter indol-derivater, så som bl.a. omtalt i publiserte franske patentsøknader nr. 8115513, 8115514, 8115515, 8309429, 8418618, 8511790, 8518416, 8517858, 8700107, 8700108, 8708193 og europeisk patentsøknad, publikasjon nr. 147107, 237678, 242939, 244085, 225726, 254433, 303506, 303507, 354777 og 382570. Forbindelsene omtalt i patentbeskrivelsene (heretter beskrevet som forbindelser A) er egnet ved behandling av migrene og cluster headache. A number of compounds which selectively contract strips of saphenous vein isolated from dogs and which contract the carotid artery bed in anesthetized dogs have been previously described. The compounds include indole derivatives, such as i.a. Mentioned in Published French Patent applications no. 8115513, 8115514, 8115515, 8309429, 8418618, 8511790, 8518416, 8517858, 8700107, 8700108, 8708193 and European Patentage, NR. , 354777 and 382570. The compounds mentioned in the patent descriptions (hereinafter described as compounds A) are suitable for the treatment of migraine and cluster headache.
Foreliggende oppfinnelse tilveiebringer et farmasøytisk bruse-preparat for peroral bruk som omfatter et gass-utviklende par som i det vesentlige består av en basisk komponent og en sur komponent, hvilke komponenter reagerer i nærvær av vann for å utvikle en gass. Preparatet karakteriseres ved at det videre omfatter en forbindelse som tjener som SHT^-lignende reseptoragonist, eller et fysiologisk akseptabelt salt eller solvat derav, som virkestoff. The present invention provides a pharmaceutical effervescent preparation for oral use which comprises a gas-evolving pair which essentially consists of a basic component and an acidic component, which components react in the presence of water to develop a gas. The preparation is characterized by the fact that it further comprises a compound that serves as an SHT^-like receptor agonist, or a physiologically acceptable salt or solvate thereof, as active ingredient.
I en foretrukket utførelsesform av oppfinnelsen tilveiebringes et farmasøytisk bruse-preparat for peroral bruk som omfatter én eller flere av forbindelsene A eller farmasøytisk akseptable salter eller solvater derav, som virkestoff. In a preferred embodiment of the invention, a pharmaceutical effervescent preparation for oral use is provided which comprises one or more of the compounds A or pharmaceutically acceptable salts or solvates thereof, as active ingredient.
Preparater i henhold til oppfinnelsen, har fortrinnsvis en form som er tilpasset medisinsk, særlig humanmedisinsk, bruk. Preparations according to the invention preferably have a form which is adapted to medical, especially human medical, use.
Peroral administrasjon utgjør en foretrukket administrasjons-måte for forbindelsene A, og bruse-preparater utgjør en anvendelig og fordelaktig formuleringstype for peroral bruk. Før det inntas av pasienten, oppløses og/eller dispergeres bruse-preparatet i for eksempel et vandig medium, så som drikkevann. Det er ønskelig at oppløsning og/eller dispersjon skjer hurtig og under brusing for å gi en behagelig presentasjon av medikamentet, spesielt for pasienter som helst ikke vil ta tabletter eller som har vaskelig-heter med å svelge dem. Oppløsningen eller dispergeringen av bruse-preparatet gir dessuten et flytende preparat som inneholder en fast medikamentdose uten behov for at pasienten avmåler et foreskrevet volum. Vannfrie bruse-preparater i henhold til oppfinnelsen, har vist seg å ha utmerket stabilitet og formulerings-karakteristika og å oppløses og/eller dispergeres raskt i vann for å gi en akseptabel administrasjonsform av medikamentet. Oral administration constitutes a preferred method of administration for compounds A, and effervescent preparations constitute a useful and advantageous type of formulation for oral use. Before it is ingested by the patient, the fizzy preparation is dissolved and/or dispersed in, for example, an aqueous medium, such as drinking water. It is desirable that dissolution and/or dispersion take place quickly and under effervescence in order to provide a pleasant presentation of the drug, especially for patients who would prefer not to take tablets or who have trouble swallowing them. The dissolution or dispersion of the effervescent preparation also provides a liquid preparation containing a fixed drug dose without the need for the patient to measure out a prescribed volume. Anhydrous effervescent preparations according to the invention have been shown to have excellent stability and formulation characteristics and to dissolve and/or disperse quickly in water to provide an acceptable administration form of the drug.
En særlig foretrukket forbindelse for bruk i preparatene i henhold til foreliggende oppfinnelse, er 3-[2-(dimetylamino)etyl]-N-metyl-lH-indol-5-metansulfonamid. A particularly preferred compound for use in the preparations according to the present invention is 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulfonamide.
3-[2-(dimetylamino)etyl]-N-metyl-lH-indol-5-metansulfonamid som har formelen (I) 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulfonamide having the formula (I)
og fysiologisk akseptable salter og solvater derav, er beskrevet i fransk patentsøknad nr. 8511790. Forbindelsen med formel (I) opp-viser selektivt vasokontraherende virkning og er anvendelig ved behandling av migrene. Fransk patentsøknad nr. 8511790 inneholder henvisninger til formuleringer for peroral administrasjon, som kan ha form av for eksempel tabletter, kapsler, granuler, pulvere, oppløsninger, siruper, suspensjoner, eller tabletter eller pastiller for buccal administrasjon. and physiologically acceptable salts and solvates thereof, are described in French patent application no. 8511790. The compound of formula (I) exhibits selective vasoconstrictive action and is applicable in the treatment of migraine. French patent application No. 8511790 contains references to formulations for oral administration, which may take the form of, for example, tablets, capsules, granules, powders, solutions, syrups, suspensions, or tablets or lozenges for buccal administration.
I "henhold til et særlig foretrukket aspekt ved foreliggende oppfinnelse, tilveiebringes således et farmasøytisk bruse-preparat for peroral bruk, som omfatter 3-[2-(dimetylamino)etyl]-N-metyl-lH-indol-5-metansulfonamid, eller et fysiologisk akseptabelt salt eller solvat derav, som virkestoff. According to a particularly preferred aspect of the present invention, a pharmaceutical effervescent preparation for oral use is thus provided, comprising 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulfonamide, or a physiologically acceptable salt or solvate thereof, as active ingredient.
Vi har funnet at 3-[2-(dimetylamino)etyl]-N-metyl-lH-indol-5-metansulfonamid, eller et fysiologisk akseptabelt salt eller solvat derav, har overraskende fordeler når det administreres i form av et bruse-preparat. We have found that 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulfonamide, or a physiologically acceptable salt or solvate thereof, has surprising advantages when administered in the form of an effervescent preparation.
Ved behandling av akutte tilstander, så som migrene, er det svært ønskelig at farmasøytiske preparater har god biotilgjenge-lighet og en raskt innsettende virkning. Bruseformuleringene i henhold til foreliggende oppfinnelse har vist seg å ha utmerkede farmakokinetiske parametere. Sammenlignet med konvensjonelle tablettformuleringer resulterer brusetablettene i at medikamentet hurtigere absorberes i plasma og kan ha en hurtigere innsettende virkning. When treating acute conditions, such as migraine, it is highly desirable that pharmaceutical preparations have good bioavailability and a fast-onset effect. The effervescent formulations according to the present invention have been shown to have excellent pharmacokinetic parameters. Compared to conventional tablet formulations, the effervescent tablets result in the drug being more quickly absorbed into the plasma and can have a faster onset of action.
Gjennom foreliggende oppfinnelse kan et pattedyr, innbefattet mennesket, som lider av, eller er utsatt for hodepine, behandles ved peroralt å administreres et farmasøytisk bruse-preparat som inneholder en forbindelse som tjener som SHT^-lignende reseptoragonist, fortrinnsvis 3-[2-(dimetylamino)etyl]-N-metyl-lH-indol-5-metansulfonamid eller et fysiologisk akseptabelt salt eller solvat derav. Through the present invention, a mammal, including humans, suffering from, or susceptible to, headaches can be treated by orally administering a pharmaceutical effervescent preparation containing a compound that serves as an SHT^-like receptor agonist, preferably 3-[2-( dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulfonamide or a physiologically acceptable salt or solvate thereof.
Tilstander som ledsager hodepine, innbefatter cluster headache, kronisk paroksysmal hemikrani, hodepine i forbindelse med vaskulære forstyrrelser, hodepine i forbindelse med stoffer eller avvenning fra slike (for eksempel medikament-avvenning), tensjonshodepine og spesielt migrene. Når det er her tale om behandling, innbefatter dette både profylaktisk anvendelse og bruk for å lindre etablerte symptomer. Conditions that accompany headache include cluster headache, chronic paroxysmal hemicrania, headache in connection with vascular disorders, headache in connection with substances or withdrawal from such (for example drug withdrawal), tension headache and especially migraine. When it comes to treatment, this includes both prophylactic use and use to relieve established symptoms.
Det er å foretrekke at 3-[2-(dimetylamino)-etyl]-N-metyl-lH-indol-5-metansulfonamid benyttes i preparatene i henhold til oppfinnelsen, i form av et fysiologisk akseptabelt salt. Slike salter innbefatter salter av uorganiske eller organiske syrer, så som hydroklorid-, hydrobromid-, sulfat-, nitrat-, fosfat-, formiat-, mesylat-, citrat-, benzoat-, fumarat-, maleat- og succinatsalter. Spesielt foretrekkes bruk av 3-[2-(dimetylamino)etyl]-N-metyl-lH-indol-5-metansulfonamid i preparatene i henhold til oppfinnelsen, i form av dens succinat (1:1) salt. It is preferable that 3-[2-(dimethylamino)-ethyl]-N-methyl-1H-indole-5-methanesulfonamide is used in the preparations according to the invention, in the form of a physiologically acceptable salt. Such salts include salts of inorganic or organic acids, such as hydrochloride, hydrobromide, sulfate, nitrate, phosphate, formate, mesylate, citrate, benzoate, fumarate, maleate and succinate salts. Particularly preferred is the use of 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulfonamide in the preparations according to the invention, in the form of its succinate (1:1) salt.
Bruseformuleringer inneholder et gass-utviklende par som i det vesentlige består av en basisk komponent og en sur komponent og som reagerer i nærvær av vann under utvikling av en gass. I preparatene i henhold til oppfinnelsen, kan basekomponenten for eksempel være et alkalimetall- eller jordalkalimetallkarbonat eller -bikarbonat, så som natriumbikarbonat, kaliumbikarbonat, magnesiumkarbonat eller kalsiumkarbonat. Syrekomponenten kan for eksempel være en alifatisk karboksylsyre eller et salt derav, så som sitronsyre og salter derav. Effervescent formulations contain a gas-evolving couple which essentially consists of a basic component and an acidic component and which reacts in the presence of water to evolve a gas. In the preparations according to the invention, the base component can for example be an alkali metal or alkaline earth metal carbonate or bicarbonate, such as sodium bicarbonate, potassium bicarbonate, magnesium carbonate or calcium carbonate. The acid component can, for example, be an aliphatic carboxylic acid or a salt thereof, such as citric acid and salts thereof.
Fortrinnsvis vil den basiske komponent i preparater i henhold til oppfinnelsen, omfatte natriumbikarbonat. Preferably, the basic component in preparations according to the invention will comprise sodium bicarbonate.
Fortrinnsvis vil den sure komponent i preparater i henhold til oppfinnelsen, omfatte mononatriumcitrat. Preferably, the acidic component in preparations according to the invention will comprise monosodium citrate.
Mengden av forbindelser som tjener som 5HT1~lignende reseptoragonister i bruse-preparatet i henhold til oppfinnelsen, vil avhenge av den aktuelle anvendte forbindelse. Den nøyaktige terapeutiske dose vil dessuten avhenge av pasientens alder og tilstand og den aktuelle lidelses natur og vil i siste instans avhenge av behandlende leges vurdering. Generelt vil mengden av en forbindelse som har SHT^-lignende aktivitet være i området fra 0,5 mg til 250 mg. Forbindelsene kan administreres for eksempel 1 til 4 ganger per dag, fortrinnsvis 1 eller 2 ganger. The amount of compounds that serve as 5HT1~-like receptor agonists in the fizzy preparation according to the invention will depend on the relevant compound used. The exact therapeutic dose will also depend on the patient's age and condition and the nature of the disorder in question and will ultimately depend on the treating doctor's assessment. Generally, the amount of a compound having SHT 2 -like activity will range from 0.5 mg to 250 mg. The compounds can be administered, for example, 1 to 4 times per day, preferably 1 or 2 times.
Mengden av 3-[2-(dimetylamino)etyl]-N-metyl-lH-indol-5-metansulfonamid, fortrinnsvis i form av et fysiologisk akseptabelt salt, benyttet i bruse-preparatene i henhold til oppfinnelsen, vil fortrinnsvis ligge i området fra 1 mg til 200 mg, helst 20 mg til 150 mg, for eksempel ca. 100 mg, beregnet som vekt av fri base. Innholdet av virkestoff i bruse-preparatet (i form av fri base eller et fysiologisk akseptabelt salt) kan for eksempel ligge i området fra 1 til 20 vekt%. The amount of 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulfonamide, preferably in the form of a physiologically acceptable salt, used in the fizzy preparations according to the invention, will preferably lie in the range from 1 mg to 200 mg, preferably 20 mg to 150 mg, for example approx. 100 mg, calculated as weight of free base. The content of active substance in the fizzy preparation (in the form of a free base or a physiologically acceptable salt) can for example be in the range from 1 to 20% by weight.
De basiske og sure komponentene kan uavhengig av hverandre, utgjøre for eksempel 25 vekt% til 55 vekt%, fortrinnsvis 35 til 45 vekt% av bruse-preparatet. Forholdet mellom sur komponent og basisk "komponent kan hensiktsmessig være i området 1:2 til 2:1, fortrinnsvis 1:1. The basic and acidic components can, independently of each other, make up, for example, 25% to 55% by weight, preferably 35 to 45% by weight, of the fizzy drink preparation. The ratio between acidic component and basic component can suitably be in the range 1:2 to 2:1, preferably 1:1.
Mange medikamenter har en naturlig bitter smak. Smaken av preparater inneholdende forbindelser som tjener som SHT-^-lignende reseptoragonister kan forbedres ved bruk av smaksstoffer og/eller søtningsmidler. Egnede smaksstoffer kan for eksempel være sitron-, appelsin-, grapefrukt- eller mintaroma. Egnede søtningsmidler" for bruk i preparatene i henhold til oppfinnelsen, innbefatter sukrose, natrium, sakkarin, cyklaminsyre og alkali- eller jordalkalimetall-salter derav, mannitol, nutrasweet R, acesulfam kalium, thaumatin eller aspartam. Ett eller flere slike smaksforbedrende midler og/ eller søtningsmidler kan benyttes. Many medicines have a naturally bitter taste. The taste of preparations containing compounds that serve as SHT-^-like receptor agonists can be improved by the use of flavorings and/or sweeteners. Suitable flavorings can be, for example, lemon, orange, grapefruit or mint flavouring. Suitable sweeteners" for use in the preparations according to the invention include sucrose, sodium, saccharin, cyclamic acid and alkali or alkaline earth metal salts thereof, mannitol, nutrasweet R, acesulfame potassium, thaumatin or aspartame. One or more such taste improving agents and/or sweeteners can be used.
Fortrinnsvis vil bruse-preparater i henhold til oppfinnelsen, inneholde aspartam som søtningsmiddel. Preferably, soda preparations according to the invention will contain aspartame as a sweetener.
Et foretrukket bruse-preparat i henhold til oppfinnelsen, omfatter 3-[2-(dimetylamino)etyl]-N-metyl-lH-indol-5-metan-sulfonamid-succinat (1:1), mononatriumcitrat og natriumbikarbonat, sammen med aspartam som søtningsmiddel. Disse fire bestanddelene kan herunder foreligge i mengder på henholdsvis 1 til 20 vekt%, 25 til 55 vekt%, 25 til 55 vekt% og 1 til 4 vekt%. A preferred soft drink preparation according to the invention comprises 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methane-sulfonamide succinate (1:1), monosodium citrate and sodium bicarbonate, together with aspartame as a sweetener. These four components can be present below in amounts of 1 to 20% by weight, 25 to 55% by weight, 25 to 55% by weight and 1 to 4% by weight, respectively.
Bruse-preparatet i henhold til oppfinnelsen, kan formuleres ved å benytte ytterligere fysiologisk akseptable bære- eller hjelpestoffer. Slike ytterligere bære- eller hjelpestoffer er fortrinnsvis vann-oppløselig eller tilnærmet vann-oppløselige, og kan for eksempel være bindemidler så som polyvinylpyrrolidon og/eller glattemidler så som natriumbenzoat eller polyalkylen-glykoler. Ett eller flere farvestoffer kan også inngå. The effervescent preparation according to the invention can be formulated by using additional physiologically acceptable carriers or auxiliary substances. Such additional carriers or auxiliary substances are preferably water-soluble or nearly water-soluble, and can for example be binders such as polyvinylpyrrolidone and/or smoothing agents such as sodium benzoate or polyalkylene glycols. One or more dyes may also be included.
Preparatene kan for eksempel ha form av tabletter, granuler eller pulvere, hvorav granuler eller pulvere hensiktsmessig forelegges som en fast dose i en liten pute. Fortrinnsvis vil preparatene ha form av tabletter. The preparations can, for example, take the form of tablets, granules or powders, of which granules or powders are conveniently presented as a fixed dose in a small pad. Preferably, the preparations will take the form of tablets.
Når bruse-preparatet formuleres som tabletter, inneholder disse fortrinnsvis 1 til 3 vekt% bindemiddel, f.eks. polyvinylpyrrolidon og 2 til 4 vekt% glattemiddel, f.eks. natriumbenzoat. Dersom brusemidlet formuleres som granuler eller pulvere i små puter, inneholder disse fortrinnsvis 2 til 4 vekt% bindemiddel, så som polyvinylpyrrolidon. When the fizzy preparation is formulated as tablets, these preferably contain 1 to 3% by weight of binder, e.g. polyvinylpyrrolidone and 2 to 4% by weight smoothing agent, e.g. sodium benzoate. If the effervescent agent is formulated as granules or powders in small pads, these preferably contain 2 to 4% by weight of binder, such as polyvinylpyrrolidone.
Bruse-preparatet i henhold til oppfinnelsen, kan fremstilles etter velkjent farmasøytisk teknikk for fremstilling av tabletter, granuler og pulvere. The effervescent preparation according to the invention can be prepared according to well-known pharmaceutical techniques for the production of tablets, granules and powders.
For fremstillingen av bruse-preparater i henhold til oppfinnelsen, kan en forbindelse som har 5HT1~lignende agonistaktivitet, eller et fysiologisk akseptabelt salt eller solvat derav, den sure komponent og den basiske komponent, blandes med passende hjelpestoffer og eventuelt granuleres. Eventuelt kan ett eller flere søtningsmidler tilsettes enten før eller etter granulering. Dersom fremstillingsprosessen inkluderer granulering, bør denne gå forut for tilsetningen av eventuelle smaksforbedrende midler. Tabletter kan fremstilles, for eksempel ved pressing av pulverblandingen eller granulatet under bruk av et glattemiddel for å lette tabletteringen. For the production of fizzy preparations according to the invention, a compound which has 5HT1-like agonist activity, or a physiologically acceptable salt or solvate thereof, the acidic component and the basic component, can be mixed with suitable excipients and optionally granulated. Optionally, one or more sweeteners can be added either before or after granulation. If the manufacturing process includes granulation, this should precede the addition of any taste-enhancing agents. Tablets can be prepared, for example, by pressing the powder mixture or the granulate using a smoothing agent to facilitate tableting.
Det er viktig at preparatet i henhold til oppfinnelsen, fremstilles, pakkes og lagres under lave fuktighetsbetingelser. Således kan for eksempel tabletter pakkes enkeltvis i forseglede strimler fremstillet av vanntett materiale, så som aluminiumfolie, eller forelegges i egnede multidosebeholdere (fremstillet av f.eks. polypropylen) som inneholder et tørkemiddel, f.eks. silika-gel. Pulveret eller granuler kan for eksempel forelegges i forseglede vanntette småputer, hensiktsmessig inneholdende en enkelt fastlagt dose. It is important that the preparation according to the invention is prepared, packaged and stored under low humidity conditions. Thus, for example, tablets can be packed individually in sealed strips made of waterproof material, such as aluminum foil, or placed in suitable multi-dose containers (made of, for example, polypropylene) containing a desiccant, e.g. silica gel. The powder or granules can, for example, be presented in sealed waterproof pouches, suitably containing a single fixed dose.
Det etterfølgende eksempel illustrerer et bruse-preparat i henhold til oppfinnelsen, hvor virkestoffet er 3-[2-(dimetyl-amino) etyl]-N-metyl-lH-indol-5-metansulfonamid-succinatsalt (1:1). Andre forbindelser som virker som agonister på SHT^-lignende reseptorer kan formuleres på tilsvarende måte. The following example illustrates a fizzy preparation according to the invention, where the active ingredient is 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulfonamide succinate salt (1:1). Other compounds that act as agonists at SHT^-like receptors can be formulated in a similar manner.
Virkestoffet, vannfritt mononatriumcitrat, natriumbikarbonat og aspartam ble blandet sammen og granulert ved tilsetning av en oppløsning av polyvinylpyrrolidonet i alkoholen. Granulatet oppnådd etter blanding ble tørket og sendt gjennom en calibrator, hvoretter de resulterende granuler ble blandet med natriumbenzoat og aromastoffer. Det granulerte materialet ble presset til tabletter ved bruk av en tabletteringsmaskin forsynt med 2 0 mm stanser. The active ingredient, anhydrous monosodium citrate, sodium bicarbonate and aspartame were mixed together and granulated by adding a solution of the polyvinylpyrrolidone in the alcohol. The granules obtained after mixing were dried and passed through a calibrator, after which the resulting granules were mixed with sodium benzoate and flavoring substances. The granulated material was pressed into tablets using a tableting machine fitted with 20 mm punches.
En roterende tabletteringsmaskin forsynt med 200 mm stanser kan også benyttes til tablettering. A rotary tableting machine equipped with 200 mm punches can also be used for tableting.
Claims (16)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO920039A NO179996C (en) | 1992-01-02 | 1992-01-02 | Sprayed preparations containing 5HT1-like receptor antagonists |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO920039A NO179996C (en) | 1992-01-02 | 1992-01-02 | Sprayed preparations containing 5HT1-like receptor antagonists |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| NO920039D0 NO920039D0 (en) | 1992-01-02 |
| NO920039L NO920039L (en) | 1993-07-05 |
| NO179996B true NO179996B (en) | 1996-10-21 |
| NO179996C NO179996C (en) | 1997-01-29 |
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| Application Number | Title | Priority Date | Filing Date |
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| NO920039A NO179996C (en) | 1992-01-02 | 1992-01-02 | Sprayed preparations containing 5HT1-like receptor antagonists |
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| Country | Link |
|---|---|
| NO (1) | NO179996C (en) |
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- 1992-01-02 NO NO920039A patent/NO179996C/en not_active IP Right Cessation
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| Publication number | Publication date |
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| NO920039L (en) | 1993-07-05 |
| NO179996C (en) | 1997-01-29 |
| NO920039D0 (en) | 1992-01-02 |
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