DK154606B - PROCEDURE FOR PREPARING A STABLE SOLUTION OF A HYDROGENERED MIDDLE DRY ALKALOID - Google Patents
PROCEDURE FOR PREPARING A STABLE SOLUTION OF A HYDROGENERED MIDDLE DRY ALKALOID Download PDFInfo
- Publication number
- DK154606B DK154606B DK228676AA DK228676A DK154606B DK 154606 B DK154606 B DK 154606B DK 228676A A DK228676A A DK 228676AA DK 228676 A DK228676 A DK 228676A DK 154606 B DK154606 B DK 154606B
- Authority
- DK
- Denmark
- Prior art keywords
- mixture
- water
- weight
- hydrogenated
- ethanol
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/48—Ergoline derivatives, e.g. lysergic acid, ergotamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dermatology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
Description
Den foreliggende opfindelse angår en fremgangsmåde til fremstilling afen til oral anvendelse stabil opløsning, som indeholder et hydrogene¬ret meldrøjealkaloid eller et salt deraf samt en monovalent alkohol ogvand, hvilken fremgangsmåde er ejendommelig ved, at ét eller flerehydrogenerede meldrøjealkaloider, syntetiske derivater og/eller saltederaf i en mængde på mindst 0,1 vægtprocent opløses i en blanding afmindst én monovalent og mindst én polyvalent, farmakologisk tolerabelalkohol og vand, hvilken opløsning indeholder højst 40 vægtprocentvand.The present invention relates to a process for the preparation of a stable solution for oral use containing a hydrogenated melon alkaloid or a salt thereof and a monovalent alcohol and water, characterized in that one or more hydrogenated melon alkaloids, synthetic derivatives and / or salts thereof in an amount of at least 0.1% by weight dissolves in a mixture at least one monovalent and at least one polyvalent, pharmacologically tolerable alcohol and water, the solution containing at most 40% by weight water.
Stabilitetsforholdene i hydrogenerede meldrøjealkaloider eller deressyntetiske derivater har i de hidtil anvendte vandige opløsninger ilang tid givet anledning til bekymring, da det hidtil med de sædvan¬lige midler - fx ved gasbehandling af ampullerne - ikke var muligt atopbevare opløsninger af hydrogenerede meldrøjealkaloider i længeretid uden tab af aktivitet.The stability conditions of hydrogenated melon alkaloids or their synthetic derivatives have long been of concern in the aqueous solutions used so far, since with the usual means - for example, by gas treatment of the vials - it was not possible to store solutions of hydrogenated melon alloys for extended periods of time. activity.
I hollandsk patentansøgning nr. 7303795 er der beskrevet farmaceuti¬ske præparater med et indhold på 0,07 vægtprocent ergonorcornin ien opløsning af ca. 12 vægtprocent 94%'s ethanol og ca. 88 vægtpro¬cent vand. En sådan opløsning er dog ikke stabil. Opløsninger afdihydroergotamin og dihydroergotoxin, som indeholder mere end 40vægtprocent vand, har desuden vist sig at undergå oxidation.In Dutch Patent Application No. 7303795, pharmaceutical compositions having a content of 0.07% by weight of ergonorcornin in a solution of approx. 12% by weight 94% ethanol and approx. 88% by weight of water. However, such a solution is not stable. In addition, solutions of dihydroergotamine and dihydroergotoxin, which contain more than 40% by weight of water, have been shown to undergo oxidation.
Det viste sig overraskende, at man ifølge opfindelsen ved anvendelseaf blandinger af mono- og polyvalente alkoholer, som kan indeholde optil 40 vægtprocent vand som opløsningsmiddel, kan fremstille stabileopløsninger af hydrogenerede meldrøjealkaloider eller deres syntetiskederivater, hvilke opløsninger er holdbare i lang tid. Resultater afdisse målinger fremgår af figur 1 og 2 (vedlagt). Af disse figurerfremgår det, at et vandindhold på 40 vægtprocent udgør en væsentliggrænseværdi for den stabiliserende virkning af blandingen. Hvispræparatet indeholder mere vand, nedbrydes de hydrogenerede er-gotalkaloider oxidativt meget hurtigt.Surprisingly, it has been found that in the invention, the use of mixtures of mono- and polyhydric alcohols, which may contain up to 40% by weight of water as solvent, can produce stable solutions of hydrogenated hydrocarbon alkaloids or their synthetic derivatives, which solutions are durable for a long time. Results of these measurements are shown in Figures 1 and 2 (enclosed). From these figures, it can be seen that a water content of 40% by weight constitutes a substantial limit value for the stabilizing effect of the mixture. If the preparation contains more water, the hydrogenated islet alkaloids are oxidatively degraded very quickly.
Den i og for sig kendte og besværlige gasbehandling efter fyldning iampullerne kan undgås ved anvendelse af opløsningsmiddelblandingen ifølge opfindelsen. Den gasbehandling, der er beskrevet i eksempler¬ne, er en mellemliggende gasbehandling, som uden at være besværligfordelagtigt anvendes til at beskytte aktivstoffet før optagelsen i detstabiliserende medium. Denne forholdsregel tages af forsigtigheds-grunde, og den er på ingen måde nødvendig.The per se known and troublesome gas treatment after filling the vials can be avoided by using the solvent mixture according to the invention. The gas treatment described in the Examples is an intermediate gas treatment which, without being advantageously used, is used to protect the active substance prior to absorption into the stabilizing medium. This precaution is taken for precautionary reasons and is by no means necessary.
Ved fremgangsmåden ifølge opfindelsen fremstilles opløsninger, som erstabile.In the process of the invention, solutions are prepared which are stable.
Som farmakologisk tolerable organiske monovalente alkoholer kan deranvendes alkoholer med fx højst 18 carbonatomer, fortrinsvis højst 10carbonatomer, især højst 3 carbonatomer. Af disse foretrækkes isærethanol. Som farmakologisk tolerable polyvalente alkoholer anvendesalkoholer med højst 6, dog især 2 eller 3, hydroxygrupper og højst 6,dog især 2 eller 3, carbonatomer, især glycerol og propylenglycol,men der kan også forekomme polyvalente alkoholer i form af farmako¬logisk tolerable polyalkoholer, fortrinsvis polyalkylenglycoler, isærpolyethylenglycol og/eller polypropylenglycol eller blandingspolyme-risater deraf med en molekylvægt på 200-20.000, især på 200-600. Afdisse foretrækkes især en polyethylenglycol med en molekylvægt på400.As pharmacologically tolerable organic monovalent alcohols, alcohols having, for example, a maximum of 18 carbon atoms, preferably a maximum of 10 carbon atoms, especially a maximum of 3 carbon atoms can be used. Of these, ethanol is particularly preferred. As pharmacologically tolerable polyhydric alcohols, alcohols of not more than 6, but especially 2 or 3, hydroxy groups and not more than 6, but especially 2 or 3, are carbon atoms, especially glycerol and propylene glycol, but polyhydric alcohols in the form of pharmaceutically tolerable poly alcohols may also be present. preferably polyalkylene glycols, especially polyethylene glycol and / or polypropylene glycol or mixture polymers thereof having a molecular weight of 200-20,000, especially of 200-600. Particularly preferred is a polyethylene glycol having a molecular weight of 400.
Såfremt én af de ifølge opfindelsen anvendte mono- eller polyvalentealkoholer er fast ved anvendelsestemperaturen, anvendes hensigts¬mæssigt en ved denne temperatur flydende alkohol som yderligereopløsningsmiddel.If one of the mono- or polyvalent alcohols used according to the invention is solid at the temperature of use, an alcohol liquid at this temperature is suitably used as an additional solvent.
I blandingen bestående af en monovalent og en polyvalent alkohol, fxen blanding af ethanol og propylenglycol, skal de monovalente ogpolyvalente alkoholer forekomme i et vægtforhold på 1:0,1-100, isærpå 1:2.In the mixture consisting of a monovalent and a polyhydric alcohol, for example a mixture of ethanol and propylene glycol, the monovalent and polyhydric alcohols should be present in a weight ratio of 1: 0.1-100, especially 1: 2.
Opløsningerne kan naturligvis indeholde flere mono- og/eller polyva¬lente alkoholer.The solutions can, of course, contain several mono- and / or polyhydric alcohols.
Opløsningerne kan endvidere som tilsætningsstoffer indeholde farma¬kologisk tolerable organiske estere og ethere, især af de ovenfor anførte mono- og polyvalente alkoholer med fedtsyrer med 12-18carbonatomer, fx stearinsyre, palmitinsyre og oliesyre, eller fedtal¬koholer med 12-18 carbonatomer, fx laurylalkohol, cetylalkohol ogstearylalkohol.The solutions may further contain, as additives, pharmacologically tolerable organic esters and ethers, in particular of the above mono- and polyhydric alcohols with fatty acids having 12-18 carbon atoms, e.g., stearic acid, palmitic acid and oleic acid, or fatty alcohols having 12-18 carbon atoms, e.g. lauryl alcohol, cetyl alcohol and stearyl alcohol.
Opløsningerne kan ligeledes indeholde små mængder vand, men vandetmå ikke forekomme i en andel, som overstiger 40 vægtprocent, isærhøjst 3 vægtprocent, af den totale blanding.The solutions may also contain small amounts of water, but water may not be present in a proportion exceeding 40% by weight, especially not more than 3% by weight, of the total mixture.
Ved fremgangsmåden ifølge opfindelsen anvendelige hydrogeneredemeldrøjealkaloider og syntetiske derivater deraf er fx dihydroergot-amin, dihydroergocristin, dihydroergocryptin, dihydroergocornin ogblandinger deraf, især en blanding af dihydroergocristin, dihydro¬ergocryptin og dihydroergocornin i forholdet 1:1:1. Som salte an¬vendes hensigtsmæssigt salte med tolerable syrer, fx methansulfo-nater, maleinater og tartrater.Hydrogen-low-mercury alkaloids and synthetic derivatives useful in the process of the invention are, for example, dihydroergotamine, dihydroergocristine, dihydroergocryptin, dihydroergocornin and mixtures thereof, in particular a mixture of dihydroergocristine, dihydroergocryptin and dihydroergocornine: Suitable salts are used as salts with tolerable acids, for example methanesulfonates, maleinates and tartrates.
Selv om koncentrationen af de hydrogenerede meldrøjealkaloider ogderivater deraf og salte deraf samt af methergin og salte deraf ikkeer kritisk i opløsningerne, er det anbefalelsesværdigt at anvendeopløsninger med en aktivstofkoncentration på 0,1-1 vægtprocent,fortrinsvis 0,1-0,5 vægtprocent. Det er klart, at den anvendte kon¬centration afhænger af det foreliggende anvendelsesformål.Although the concentration of the hydrogenated melon alkaloids and their derivatives and salts thereof, and of the methergin and salts thereof, is not critical in the solutions, it is advisable to use solutions having an active substance concentration of 0.1-1% by weight, preferably 0.1-0.5% by weight. It is clear that the concentration used depends on the present application.
Opløsningerne kan desuden indeholde opløselighedsfremmende tilsæt¬ningsstoffer, fx syrer, især methansulfonsyre, maleinsyre eller vin¬syre.The solutions may additionally contain solubility promoting additives, for example acids, especially methanesulfonic acid, maleic acid or tartaric acid.
Fremstillingen af de omhandlede opløsninger foretages hensigtsmæssigtved opløsning af de hydrogenerede meldrøjealkaloider og derivaterderaf eller salte deraf eller af methergin eller salte deraf i et af deovenfor beskrevne opløsningsmidler eller blandinger deraf, hensigts¬mæssigt under en atmosfære af inertgas, fx under nitrogenatmosfære,hensigtsmæssigt under udelukkelse af dagslys, sædvanligvis vedstuetemperatur (15-25°C) og under omrøring.The preparation of the solutions in question is conveniently carried out by dissolving the hydrogenated hydrocarbon alkaloids and derivatives thereof or salts thereof or of methergin or salts thereof in one of the above-described solvents or mixtures thereof, suitably under an inert gas atmosphere, e.g. daylight, usually room temperature (15-25 ° C) and with stirring.
Fremstillingen af opløsningsmiddelblandingerne foretages på i og forsig kendt måde, hvorhos det er hensigtsmæssigt at udføre fremstillin¬gen af opløsningsmiddelblandingerne ved højere temperaturer, dvs. optil ca. 80°C, såfremt én af opløsningsmiddel komponenterne er fast vedstuetemperatur. Blandingsforholdene mellem de enkelte blandingskom¬ponenter er ikke kritiske. Fordelagtigt anvendes der ethanol somblandingskomponent, men det er dog ikke tvingende nødvendigt.The preparation of the solvent mixtures is carried out in a manner well known in the art, whereby it is convenient to carry out the preparation of the solvent mixtures at higher temperatures, ie. up to approx. 80 ° C, if one of the solvent components is fixed boiler temperature. The mixing ratios between the individual mixing components are not critical. Advantageously, ethanol is used as a blend component, but it is not imperative.
Opfindelsen belyses nærmere ved nedenstående eksempler: EKSEMPEL 1The invention is further illustrated by the following examples: EXAMPLE 1
Der fremstilles en blanding af 50,0 g propylenglycol og 41,9 g ethanol(94%'s renhed), og i denne blanding opløses under omrøring og undernitrogenatmosfære ved stuetemperatur 0,1 g af en blanding af dihy-droergocristin, dihydroergocryptin og dihydroergocornin i forholdet1:1:1. Efter trykfiltrering foretages aftapning på dråbeflasker.A mixture of 50.0 g of propylene glycol and 41.9 g of ethanol (94% purity) is prepared, and in this mixture at room temperature 0.1 g of a mixture of dihydroergocristine, dihydroergocryptin and dihydroergocornin is dissolved. in the ratio of 1: 1: 1. After pressure filtration, bottling is carried out on drop bottles.
EKSEMPEL 2EXAMPLE 2
Der fremstilles en blanding af 40,0 g propylenglycol, 34,0 g ethanol(94%'s renhed) og 25,0 g vandfrit glycerol, og i denne blandingopløses under omrøring og under nitrogenatmosfære ved stuetempera¬tur 0,1 g af en blanding af dihydroergocristin, dihydroergocryptin ogdihydroergocornin i forholdet 1:1:1. Efter trykfiltrering foretagesaftapning på dråbeflasker.A mixture of 40.0 g of propylene glycol, 34.0 g of ethanol (94% purity) and 25.0 g of anhydrous glycerol is prepared, and in this mixture dissolved under stirring and under nitrogen atmosphere at room temperature 0.1 g of a mixture of dihydroergocristine, dihydroergocryptin and dihydroergocornin in a 1: 1: 1 ratio. After pressure filtration, bottling is done on drop bottles.
EKSEMPEL 3EXAMPLE 3
Der fremstilles en blanding af 50,0 g propylenglycol og 41,9 g ethanol(94%'s renhed), og i denne blanding opløses under omrøring og undernitrogenatmosfære ved stuetemperatur 0,1 g dihydroergotamin-methan-sulfonat. Efter trykfiltrering foretages aftapning på dråbeflasker.A mixture of 50.0 g of propylene glycol and 41.9 g of ethanol (94% purity) is prepared, and in this mixture, 0.1 g of dihydroergotamine-methanesulfonate is dissolved under stirring and sub-nitrogen atmosphere. After pressure filtration, bottling is carried out on drop bottles.
EKSEMPEL 4EXAMPLE 4
Der fremstilles en blanding af 330 g propylenglycol, 280 g ethanol(94%'s renhed), 206 g vandfrit glycerol og 188 g demineraliseretvand, og i denne blanding opløses under omrøring og under nitrogen¬atmosfære ved stuetemperatur 1,0 g af en blanding af methansulfona-terne af dihydroergocristin, dihydroergocryptin og dihydroergocornini forholdet 1:1:1. Efter trykfiltrering foretages aftapning på dråbefla¬sker.A mixture of 330 g of propylene glycol, 280 g of ethanol (94% purity), 206 g of anhydrous glycerol and 188 g of demineralized water is prepared and in this mixture dissolved under stirring and under nitrogen at room temperature 1.0 g of a mixture of the methanesulfonates of dihydroergocristine, dihydroergocryptin and dihydroergocornini 1: 1: 1 ratio. After pressure filtration, bottling is done on drop bottles.
EKSEMPEL 5EXAMPLE 5
Der fremstilles en blanding af 293 g propylenglycol, 249 g ethanol(94%'s renhed), 183 g vandfrit glycerol og 282 g demineraliseret vand, og i denne blanding opløses under omrøring og under nitrogen¬atmosfære ved stuetemperatur 2,0 g dihydroergotamin-methansulfonat.Efter trykfiltrering foretages aftapning på dråbeflasker.A mixture of 293 g of propylene glycol, 249 g of ethanol (94% purity), 183 g of anhydrous glycerol and 282 g of demineralized water is prepared, and in this mixture dissolved under stirring and under nitrogen at room temperature 2.0 g of dihydroergotamine. methane sulfonate.After pressure filtration, bottling is dropped.
EKSEMPEL 6EXAMPLE 6
Der fremstilles en blanding af 255 g propylenglycol, 216 ;g ethanol(94%'s renhed), 159 g vandfrit glycerol og 382 g demineraliseret vand, og i denne blanding opløses under omrøring og under nitrogen¬atmosfære ved stuetemperatur 1,0 g af en blanding af methansulfona-terne af dihydroergocristin, dihydroergocryptin og dihydroergocornini forholdet 1:1:1. Efter trykfiltrering foretages aftapning på dråbefla¬sker.A mixture of 255 g of propylene glycol, 216 g of ethanol (94% purity), 159 g of anhydrous glycerol and 382 g of demineralized water is prepared, and in this mixture dissolved under stirring and under nitrogen atmosphere at room temperature 1.0 g of a mixture of the methanesulfonates of dihydroergocristine, dihydroergocryptin and dihydroergocornini ratio 1: 1: 1. After pressure filtration, bottling is done on drop bottles.
EKSEMPEL 7EXAMPLE 7
Der fremstilles en blanding af 268 g propylenglycol, 227,70 g ethanol(94%’s renhed), 167,60 g vandfrit glycerol og 335,70 g demineraliseretvand, og i denne blanding opløses under omrøring og under nitrogen¬atmosfære ved stuetemperatur 1,0 g af en blanding af methansulfona- terne af dihydroergocristin, dihydroergocryptin og dihydroergocornini forholdet 1:1:1. Efter trykfiltrering foretages aftapning på dråbefla¬sker.A mixture of 268 g of propylene glycol, 227.70 g of ethanol (94% purity), 167.60 g of anhydrous glycerol and 335.70 g of demineralized water is prepared and dissolved in this mixture under stirring and under nitrogen atmosphere at room temperature 1 , 0 g of a mixture of the methanesulfonates of dihydroergocristine, dihydroergocryptin and dihydroergocornini 1: 1: 1 ratio. After pressure filtration, bottling is done on drop bottles.
EKSEMPEL 8EXAMPLE 8
Der fremstilles en blanding af 245,80 g propylenglycol, 261,60 gethanol (94%'s renhed), 245,80 g vandfrit glycerol og 245,80 g demi¬neraliseret vand, og i denne blanding opløses under om røring ogunder nitrogenatmosfære ved stuetemperatur 1,0 g af en blanding afmethansulfonaterne af dihydroergocristin, dihydroergocryptin ogdihydroergocornin i forholdet 1:1:1. Efter trykfiltrering foretagesaftapning på dråbeflasker.A mixture of 245.80 g of propylene glycol, 261.60 g of ethanol (94% purity), 245.80 g of anhydrous glycerol and 245.80 g of demineralized water is prepared, and in this mixture is dissolved under stirring and under nitrogen atmosphere at room temperature 1.0 g of a mixture of the methanesulfonates of dihydroergocristine, dihydroergocryptin and dihydroergocornin in a ratio of 1: 1: 1. After pressure filtration, bottling is done on drop bottles.
EKSEMPEL 9EXAMPLE 9
Der fremstilles en blanding af 350,70 g propylenglycol, 297,80 g ethanol C94%'s renhed), 219,0 g vandfrit glycerol og 131,5 g deminera¬liseret vand, og i denne blanding opløses under omrøring og undernitrogenatmosfære ved stuetemperatur 1,0 g af en blanding af methan¬sulfonaterne af dihydroergocristin, dihydroergocryptin og dihydroer¬gocornin i forholdet 1:1:1. Efter trykfiltrering foretages aftapning pådråbeflasker.A mixture of 350.70 g of propylene glycol, 297.80 g of ethanol (C94% purity), 219.0 g of anhydrous glycerol and 131.5 g of demineralized water is prepared, and in this mixture is dissolved under stirring and sub-nitrogen atmosphere at room temperature. 1.0 g of a mixture of the methanesulfonates of dihydroergocristine, dihydroergocryptin and dihydroergocristine in a 1: 1: 1 ratio. After pressure filtration, drip bottles are drained.
EKSEMPEL 10EXAMPLE 10
Der fremstilles en blanding af 391,70 g propylenglycol, 332,80 g ethanol (94%'s renhed), 244,90 g vandfrit glycerol og 29,60 g demine¬raliseret vand, og i denne blanding opløses under omrøring og undernitrogenatmosfære ved stuetemperatur 1,0 g af en blanding af methan¬sulfonaterne af dihydroergocristin, dihydroergocryptin og dihydroer¬gocornin i forholdet 1:1:1. Efter trykfiltrering foretages aftapning pådråbeflasker.A mixture of 391.70 g of propylene glycol, 332.80 g of ethanol (94% purity), 244.90 g of anhydrous glycerol and 29.60 g of demineralized water is prepared, and in this mixture is dissolved under stirring and sub-nitrogen atmosphere at room temperature 1.0 g of a mixture of the methanesulfonates of dihydroergocristine, dihydroergocryptin and dihydroergocristine in a 1: 1: 1 ratio. After pressure filtration, drip bottles are drained.
Claims (3)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2524184 | 1975-05-31 | ||
| DE2524184 | 1975-05-31 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK228676A DK228676A (en) | 1976-12-01 |
| DK154606B true DK154606B (en) | 1988-12-05 |
| DK154606C DK154606C (en) | 1989-05-01 |
Family
ID=5947910
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK228676A DK154606C (en) | 1975-05-31 | 1976-05-24 | PROCEDURE FOR PREPARING A STABLE SOLUTION OF A HYDROGENERED MIDDLE DRY ALKALOID |
Country Status (26)
| Country | Link |
|---|---|
| JP (1) | JPS585167B2 (en) |
| AT (1) | AT355725B (en) |
| AU (1) | AU508625B2 (en) |
| BE (1) | BE842348A (en) |
| CA (1) | CA1069438A (en) |
| CS (1) | CS205023B2 (en) |
| DD (1) | DD125597A5 (en) |
| DK (1) | DK154606C (en) |
| ES (1) | ES448372A1 (en) |
| FI (1) | FI761461A (en) |
| FR (1) | FR2313059A1 (en) |
| GB (1) | GB1539083A (en) |
| GR (1) | GR60264B (en) |
| HK (1) | HK15383A (en) |
| HU (1) | HU171514B (en) |
| IE (1) | IE42999B1 (en) |
| IL (1) | IL49668A (en) |
| MY (1) | MY8300013A (en) |
| NL (1) | NL172616C (en) |
| NO (1) | NO145262C (en) |
| NZ (1) | NZ180984A (en) |
| PT (1) | PT65151B (en) |
| SE (1) | SE426782B (en) |
| SU (2) | SU677664A3 (en) |
| YU (1) | YU133076A (en) |
| ZA (1) | ZA763138B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2935515A1 (en) * | 1979-09-03 | 1981-03-19 | Fa. Dr. Willmar Schwabe, 7500 Karlsruhe | MEDICINAL PRODUCT |
| FR2483235A1 (en) * | 1980-05-28 | 1981-12-04 | Fabre Sa Pierre | TOPICAL COMPOSITIONS CONTAINING RYE AND VINCA ROSEA ERGOT ALKALOIDS FOR THE TREATMENT OF HYPERSEBORRHOES |
| DE3227122A1 (en) * | 1982-07-20 | 1984-01-26 | Dr. Rentschler Arzneimittel Gmbh & Co, 7958 Laupheim | STABLE SOLUTIONS OF MOTHER CORNAL CALOIDS |
| HU192050B (en) * | 1983-04-22 | 1987-05-28 | Sandoz Ag | Process for production of medical preparative containing co-dergocrin and one piridin-dicarbonic acid diesthertype calcium-antagonist |
| IT1200609B (en) * | 1985-04-04 | 1989-01-27 | Poli Ind Chimica Spa | PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF CEREBROVASCULAR TURBES AND THE ELDERLY BRAIN |
| DE102007014947B4 (en) | 2007-03-23 | 2010-05-27 | Axxonis Pharma Ag | Stabilized aqueous solutions of ergoline compounds |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DD43402A (en) * |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2033921A (en) * | 1931-08-28 | 1936-03-17 | Squibb & Sons Inc | Solution of ergot alkaloids |
| US1969382A (en) * | 1932-05-21 | 1934-08-07 | Squibb & Sons Inc | Preparation of a stable hydro-alcoholic extract of ergot |
-
1976
- 1976-05-24 DK DK228676A patent/DK154606C/en not_active IP Right Cessation
- 1976-05-24 SE SE7605841A patent/SE426782B/en not_active IP Right Cessation
- 1976-05-24 NO NO761760A patent/NO145262C/en unknown
- 1976-05-24 FI FI761461A patent/FI761461A/fi not_active Application Discontinuation
- 1976-05-25 FR FR7615744A patent/FR2313059A1/en active Granted
- 1976-05-26 GB GB21809/76A patent/GB1539083A/en not_active Expired
- 1976-05-26 ZA ZA00763138A patent/ZA763138B/en unknown
- 1976-05-27 IL IL49668A patent/IL49668A/en unknown
- 1976-05-28 AT AT390476A patent/AT355725B/en not_active IP Right Cessation
- 1976-05-28 AU AU14422/76A patent/AU508625B2/en not_active Expired
- 1976-05-28 CA CA253,612A patent/CA1069438A/en not_active Expired
- 1976-05-28 PT PT65151A patent/PT65151B/en unknown
- 1976-05-28 JP JP51062848A patent/JPS585167B2/en not_active Expired
- 1976-05-28 IE IE1138/76A patent/IE42999B1/en unknown
- 1976-05-28 NL NLAANVRAGE7605745,A patent/NL172616C/en not_active IP Right Cessation
- 1976-05-28 DD DD193077A patent/DD125597A5/xx unknown
- 1976-05-28 BE BE167442A patent/BE842348A/en not_active IP Right Cessation
- 1976-05-28 NZ NZ180984A patent/NZ180984A/en unknown
- 1976-05-29 GR GR50841A patent/GR60264B/en unknown
- 1976-05-29 ES ES448372A patent/ES448372A1/en not_active Expired
- 1976-05-31 SU SU762362650A patent/SU677664A3/en active
- 1976-05-31 CS CS763620A patent/CS205023B2/en unknown
- 1976-05-31 SU SU762362650D patent/SU952106A3/en active
- 1976-05-31 HU HU76SA00002923A patent/HU171514B/en not_active IP Right Cessation
- 1976-05-31 YU YU01330/76A patent/YU133076A/en unknown
-
1983
- 1983-05-12 HK HK153/83A patent/HK15383A/en unknown
- 1983-12-30 MY MY13/83A patent/MY8300013A/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DD43402A (en) * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4138565A (en) | Stable solutions and processes for their preparation | |
| ATE5852T1 (en) | THERAPEUTIC COMPOSITIONS WITH INCREASED BIOAVAILABILITY AND PROCESS FOR THEIR PREPARATION. | |
| DE833611T1 (en) | COMPOSITION CONTAINING AN ACTIVE SUBSTANCE SOLVED IN A GLASS-MAKING CARRIER AND A METHOD FOR THE PRODUCTION THEREOF | |
| DK154606B (en) | PROCEDURE FOR PREPARING A STABLE SOLUTION OF A HYDROGENERED MIDDLE DRY ALKALOID | |
| Beroza | Alkaloids from Tripterygium wilfordii Hook.—Wilforine and Wilfordine1, 2 | |
| KR830008490A (en) | Method for preparing cyclic peptide | |
| US4366145A (en) | Soft gelatin capsule with a liquid ergot alkaloid center fill solution and method of preparation | |
| KR830009096A (en) | Preparation of 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7- (1-piperazinyl) -1,8-naphthyridine-3-carboxylic acid / 3 hydrate | |
| HU227400B1 (en) | 2-methyl-thieno-benzodiazepine formulation and its use | |
| WO2020178725A1 (en) | Stable liquid composition of cyclophosphamide | |
| GB918600A (en) | Improvements in aqueous formaldehyde compositions | |
| CS203199B2 (en) | Method of making stabil solutions of hydrogenous ergot alcaloids,event.synthetic derivatives thereof | |
| NO853856L (en) | PROCEDURE FOR THE PREPARATION OF 1H-INDOL-3-YL CONTENT OF THE 1,3-DIMETHYL-1H-PURIN-2,6-DIONE. | |
| RU2084226C1 (en) | Composition exhibiting antitumor action | |
| US4402949A (en) | Stable solutions of hydrogenated ergotalkaloids | |
| MX165733B (en) | METHOD FOR PREPARING WATER SOLUBLE COMPLEX FROM ESSENTIALLY INSOLUBLE IN WATER ORGANIC COMPOUNDS | |
| Shamma et al. | A new group of isoquinoline alkaloids: The secoberbines | |
| Thomas | CXXV.—Inorganic complex salts. Part I. Potassium ferrioxalate and potassium cobaltimalonate | |
| GB378858A (en) | Improvements in the production of artificial materials, by wet spinning processes | |
| Hager et al. | Oxazolopyrimidine and thiazolopyrimidine derivatives related to the xanthines | |
| CZ181195A3 (en) | Pharmaceutical preparation for reducing blood pressure and process for preparing thereof | |
| US3647655A (en) | Process for the preparation of lumilysergic acid derivatives | |
| HU181940B (en) | Process for producing solutions of vincane derivatives for parentheral application | |
| SU17206A1 (en) | The method of obtaining salts of quinine or cinchonin with 3-acetyl-amino-4-hydroxyphenylarsinic acid | |
| US2390575A (en) | Stabilized solutions of ergot alkaloidal salts |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PBP | Patent lapsed |