DE889747C - Process for the preparation of aqueous solutions of theophylline - Google Patents
Process for the preparation of aqueous solutions of theophyllineInfo
- 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
- preparation
- sodium
- 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
Links
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 title claims description 58
- 229960000278 theophylline Drugs 0.000 title claims description 30
- 238000000034 method Methods 0.000 title claims description 4
- 239000007864 aqueous solution Substances 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title claims description 3
- 239000000243 solution Substances 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 4
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- QVGLHVDBDYLFON-UHFFFAOYSA-M sodium;1,3-dimethylpurin-7-ide-2,6-dione Chemical group [Na+].O=C1N(C)C(=O)N(C)C2=C1[N-]C=N2 QVGLHVDBDYLFON-UHFFFAOYSA-M 0.000 description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 229960004025 sodium salicylate Drugs 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000006173 Good's buffer Substances 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, 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
- C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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:
Claims (2)
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)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0173240A2 (en) * | 1984-08-29 | 1986-03-05 | Asche Aktiengesellschaft | Injectable solution |
-
1952
- 1952-01-01 DE DEK12667A patent/DE889747C/en not_active Expired
Cited By (2)
| 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 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE889747C (en) | Process for the preparation of aqueous solutions of theophylline | |
| EP0319598A1 (en) | Stabilized aqueous preparation of folic acid | |
| DE2138049C3 (en) | Salts the 7-square bracket on D-2'-phenyl-2'-aminoacetamido square bracket to-desacetoxycephalosporanic acid | |
| DE709176C (en) | Process for the production of long-life aqueous solutions containing k-strophanthin, theophylline and grape sugar | |
| DE604228C (en) | Process for the preparation of easily soluble in water preparations of the salts of the china alkaloids which are difficult to dissolve or insoluble in water or of their aqueous solutions | |
| DE1196629B (en) | Process for the production of nonionic, therapeutically usable ferric hydroxide-dextran complexes | |
| DE977478C (en) | Process for the manufacture of injectable insulin preparations with delayed action | |
| DE2241076B2 (en) | Tetracycline complex and its salts, process for its preparation and pharmaceutical compositions containing this complex | |
| DE629841C (en) | Process for the preparation of an aqueous quinine solution for injection purposes | |
| DE1028262B (en) | Process for improving the flowability of phosphors | |
| DE725439C (en) | Process for the production of stable, neutral solutions of the blood sugar lowering hormone of the pancreatic gland | |
| DE933450C (en) | Process for the preparation of a new salt of penicillin G. | |
| DE938249C (en) | Process for the preparation of dihydrocodeine hydrorhodanide | |
| DE862341C (en) | Process for the preparation of aqueous solutions of derivatives of p-aminobenzene sulfonamide | |
| DE321616C (en) | Process for the preservation of hydrogen peroxide solutions | |
| DE852083C (en) | Process for the production of alkali thick liquors that remain water-white when diluted | |
| DE726888C (en) | Process for the preparation of solutions or suspensions of the blood sugar lowering hormone of the pancreatic gland | |
| DE642245C (en) | Process for the production of neutral soluble metal complex salts | |
| DE936592C (en) | Process for the production of a blood and urine sugar lowering preparation from trioxyflavone glucoside-containing parts of plants | |
| DE682021C (en) | Process for the preparation of durable complex gold compounds of catechol disulfonic acid | |
| DE425419C (en) | Process for the production of aromatic stibic acids | |
| DE646595C (en) | Process for making a laxative | |
| AT234908B (en) | Process for the production of water-soluble complex compounds of the rare earth metals | |
| DE711635C (en) | Process for stabilizing solutions of the circulatory hormone kallikrein from pancreas | |
| DE655684C (en) | Process for the production of metal compounds of keratinic acids |