DE889747C - Process for the preparation of aqueous solutions of theophylline - Google Patents

Process for the preparation of aqueous solutions of theophylline

Info

Publication number
DE889747C
DE889747C DEK12667A DEK0012667A DE889747C DE 889747 C DE889747 C DE 889747C DE K12667 A DEK12667 A DE K12667A DE K0012667 A DEK0012667 A DE K0012667A DE 889747 C DE889747 C DE 889747C
Authority
DE
Germany
Prior art keywords
theophylline
solutions
sodium
solution
aqueous solutions
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
DEK12667A
Other languages
German (de)
Inventor
Karl Dr Wulzinger
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Knoll GmbH
Original Assignee
Knoll GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Knoll GmbH filed Critical Knoll GmbH
Priority to DEK12667A priority Critical patent/DE889747C/en
Application granted granted Critical
Publication of DE889747C publication Critical patent/DE889747C/en
Expired legal-status Critical Current

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D473/00Heterocyclic compounds containing purine ring systems
    • C07D473/02Heterocyclic compounds containing purine ring systems with oxygen, sulfur or nitrogen atoms directly attached in positions 2 and 6
    • C07D473/04Heterocyclic compounds containing purine ring systems with oxygen, sulfur or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
    • C07D473/06Heterocyclic compounds containing purine ring systems with oxygen, sulfur or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
    • C07D473/08Heterocyclic compounds containing purine ring systems with oxygen, sulfur or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline

Description

Verfahren zur Herstellung von wässerigen Losungen des Theophyllins Theophyllin ist in Wasser zu nur o,5 °/o löslich. Zur Gewinnung von höherprozentigen wäßrigen Theophyllinlösungen wurde schon vorgeschlagen, Theophyllinnatriuan oder dementsprechend molekulare Mengen von Theophyllin und Natriumhydroxyd mit Natriumacetat oder Natriumsalicylat zu kombinieren. Die Löslichkeitserhöhung des Theophyllins ist aber nach diesem Vorschlag eine beschränkte, da eine gesättigte Theophyllinnatriumlösung nur etwa q. °/o Theophyllin enthält. In der Therapie ist diese Lösung infolge ihrer stark alkalischen Reaktion (pH zz bis 12) ebenfalls nur beschränkt verwendbar. Ferner wird durch die Kombinierung mit Natriumsalicylat bzw. Natriumacetat die Löslichkeit des Theophyllinnatriums zufolge der Vermehrung der Natriumionen zurückgedrängt. Nach anderen Vorschlägen werden organische Basen als Lösungsvermittler für Theophyllin verwendet. Solche Lösungen haben den Nachteil, daß die meist großen Mengen der Lösungsvermittler zu Theophyllin häufig keine Synergisten darstellen oder selbst unwirksam sind und damit für die Lösungen einen unerwünschten Ballast darstellen.Process for the preparation of aqueous solutions of theophylline Theophylline is only 0.5% soluble in water. For the extraction of higher percentage aqueous theophylline solutions have already been proposed, theophylline natriuan or accordingly, molecular amounts of theophylline and sodium hydroxide with sodium acetate or to combine sodium salicylate. The increase in solubility of theophylline but according to this proposal it is a limited one, since it is a saturated theophylline sodium solution only about q. ° / o contains theophylline. In therapy this solution is due to their strongly alkaline reaction (pH zz up to 12) can also only be used to a limited extent. Further the combination with sodium salicylate or sodium acetate increases the solubility of theophylline sodium due to the increase in sodium ions. According to other proposals, organic bases are used as solubilizers for theophylline used. Such solutions have the disadvantage that the mostly large amounts of solubilizers to theophylline often do not represent synergists or are themselves ineffective and thus represent an undesirable ballast for the solutions.

Es wurde nun gefunden, daß man therapeutisch brauchbare wäßrige Theophyllinlösungen dadurch erhält, daß man Theophyllin mit weniger als der dem molekularen Verhältnis r : z entsprechenden Menge Alkalihydroxyd zur Lösung bringt oder Theophyllin in Theophyllinalkalilösungen auflöst, wobei mehr als die Hälfte der molekularen Menge vom Theophyllinalkali an Theophyllin in Lösung geht. Diese Lösungen enthalten also die Alkalisalze der sehr schwachen Säure Theophyllin neben dieser Säure selbst, deren saure Dissoziationskonstante 1,69 . io-o (25°) beträgt; sie bilden gute Puffersysteme, deren pH leicht auf 9 bis io gebracht wird. Gegenüber reinen Theophyllinnatriumlösungen z. B. mit einem p#I von ii bis 12 ist das ph der erfindungsgemäßen Lösungen um 2 Einheiten gesenkt bei nur geringem Ballast an Alkaliionen; die Lösungen sind daher für die therapeutische Verwendung, insbesondere auch für Injektionszwecke geeignet. Ihr Theophyllingehalt kann bis auf ioo/o und darüber erhöht werden.It has now been found that therapeutically useful aqueous theophylline solutions can be obtained by obtaining theophylline with less than that of the molecular ratio r: z brings the appropriate amount of alkali hydroxide to solution or theophylline in Theophylline alkaline solutions dissolve, being more than half the molecular amount from theophylline alkali to theophylline goes into solution. So these solutions contain the alkali salts of the very weak Acid theophylline in addition to this Acid itself, its acidic dissociation constant 1.69. io-o (25 °); she form good buffer systems, the pH of which can easily be brought to 9 to 10. Opposite to pure theophylline sodium solutions z. B. with a p # I from ii to 12 the ph is the Solutions according to the invention reduced by 2 units with only little ballast of alkali ions; The solutions are therefore for therapeutic use, especially for Suitable for injections. Their theophylline content can be up to 100 per cent and above increase.

Beispiele i. 8,25 g Theophyllin . H20 und i g Natriumhydroxyd werden zu ioo g mit Wasser aufgefüllt und gelöst. Die gleiche Lösung erhält man, wenn man 3,3 g Theophyllin zusammen mit 5,5 g Theophyllinnatrium und Wasser zu ioo g zur Lösung bringt. Der Natriumgehalt der Lösung beträgt 0,575 °/o.Examples i. 8.25 g theophylline. H20 and ig sodium hydroxide are made up to 100 g with water and dissolved. The same solution is obtained if one brings 3.3 g theophylline together with 5.5 g theophylline sodium and water to 100 g to the solution. The sodium content of the solution is 0.575% .

2. Folgende Gewichtsmengen Theophyllin und Theophyllinkalium werden mit Wasser zu ioo g aufgefüllt und gelöst: g Theo- g Theophyllin- Theophyllingehalt. phyllin # H20 kalium # H20 der Lösung in Prozent a) 3,i 5,5 7,7 b) 5,3 1o 13,7 c) 8,4 18 23,5 Die pH-Werte der Lösungen liegen zwischen 9 und io, mit Glaselektrode bei 2o° gemessen. An Stelle von Theophyllinkalium können die entsprechenden Mengen Theophyllin und Kaliumhydroxyd angewandt werden.2. The following amounts by weight of theophylline and theophylline potassium are made up to 100 g with water and dissolved: g theog theophylline-theophylline content. phyllin # H20 potassium # H20 of the solution in percent a) 3, i 5.5 7.7 b) 5.3 1o 13.7 c) 8.4 18 23.5 The pH values of the solutions are between 9 and 10, measured with a glass electrode at 20 °. Instead of potassium theophylline, the appropriate amounts of theophylline and potassium hydroxide can be used.

Claims (2)

PATENTANSPRÜCHE: i. Verfahren zur Herstellung von wäßrigen Lösungen des Theophyllins, dadurch gekennzeichnet, daß man Theophyllin in Gegenwart von Theophyllinalkali und Wasser löst. PATENT CLAIMS: i. Process for the preparation of aqueous solutions of theophylline, characterized in that theophylline in the presence of theophylline alkali and water dissolves. 2. Verfahren nach Anspruch i, dadurch gekennzeichnet, daß man Theophyltin mit weniger als der dem molekularen Verhältnis i : i entsprechenden Menge Alkalihydroxyd zur Lösung bringt, vorzugsweise im Molverhältnis von Theophyllinalkali : Theophyllin = i : o, 5.2. The method according to claim i, characterized in that theophyltin with less than the amount of alkali metal hydroxide corresponding to the molecular ratio i: i brings to solution, preferably in the molar ratio of theophylline alkali: theophylline = i: o, 5.
DEK12667A 1952-01-01 1952-01-01 Process for the preparation of aqueous solutions of theophylline Expired DE889747C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DEK12667A DE889747C (en) 1952-01-01 1952-01-01 Process for the preparation of aqueous solutions of theophylline

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DEK12667A DE889747C (en) 1952-01-01 1952-01-01 Process for the preparation of aqueous solutions of theophylline

Publications (1)

Publication Number Publication Date
DE889747C true DE889747C (en) 1953-09-14

Family

ID=7213869

Family Applications (1)

Application Number Title Priority Date Filing Date
DEK12667A Expired DE889747C (en) 1952-01-01 1952-01-01 Process for the preparation of aqueous solutions of theophylline

Country Status (1)

Country Link
DE (1) DE889747C (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0173240A2 (en) * 1984-08-29 1986-03-05 Asche Aktiengesellschaft Injectable solution

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0173240A2 (en) * 1984-08-29 1986-03-05 Asche Aktiengesellschaft Injectable solution
EP0173240A3 (en) * 1984-08-29 1987-06-24 Asche Aktiengesellschaft Injectable solution

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