DEP0053941DA - - Google Patents
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- Publication number
- DEP0053941DA DEP0053941DA DEP0053941DA DE P0053941D A DEP0053941D A DE P0053941DA DE P0053941D A DEP0053941D A DE P0053941DA
- Authority
- DE
- Germany
- Prior art keywords
- ether
- water
- cresyl
- solution
- 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.)
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 238000010792 warming Methods 0.000 claims description 2
- 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 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 150000007513 acids Chemical class 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 238000009938 salting Methods 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 206010041349 Somnolence Diseases 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- FPCQPFCFOQESMK-UHFFFAOYSA-N [Na].OC(=O)C1=CC=C(O)C=C1O Chemical compound [Na].OC(=O)C1=CC=C(O)C=C1O FPCQPFCFOQESMK-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- -1 aromatic carboxylic acids Chemical class 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
Description
1.9.491.9.49
Fa.Heinrich Mack Nschf. t Illertissen/Bayern. Verfahren zur Herstellung haltbarer wässrigerHeinrich Mack Nschf. t Illertissen / Bavaria. Process for making durable aqueous
Die Verwendung von o-Kresyl-alphaglycerinäther als muskelersehlaffendes Mittel zur intramuskulären oder intravenösen Applikation erfordert die Verwendung von Gramm-Dosen. Ds dieser Stoff bei Zimmertemper8tür in Passer nur zu etwa V% löslich ist, wären Volumina notwendig, die seine Anwendung unmöglich machten. 2s ist bekennt, durch Zusatz von Harnstoff oder seinen Derivaten die Löslichkeit des o-Kresyl-alpha-glycerinäthers zu steigern. Diese Stoffe besitzen aber in pharmakologischer Hinsicht eine dem o-Kresyl-alphaglycerinäther entgegengesetzte Wirkung, sodass die therapeutische Anwendung erheblich beeinträohtigt wird.The use of o-cresyl-alphaglycerol ether as a muscle-relaxing agent for intramuscular or intravenous administration requires the use of doses of grams. Since this substance is only about V% soluble in register at room temperature, volumes would be necessary which would make its use impossible. 2s is known to increase the solubility of o-cresyl-alpha-glycerol ether by adding urea or its derivatives. In pharmacological terms, however, these substances have an effect opposite to that of o-cresyl-alphaglycerol ether, so that therapeutic use is considerably impaired.
Dieser Mangel «ird durch die Erfindung überwunden. Es wurde nämlich gefunden, dass Wasser oder wässrige Lösungen in Anwesenheit von wasserlöslichen Salzen hydroxylhaltiger aromatischer Carbonsäuren erheblich grössere Kengen von o-Kresyl-alpha-glycerinäther in klarer Lösung aufzunehmen und nach dem Abkühlen such zu hslten vermögen als reines Wasser. Die Haltbarkeit dieser Lösungen ist in verschlossenen Gefässen unbegrenzt. Auch nach noch so langem Stehen soheiden sich keine Kristalle aus.This deficiency is overcome by the invention. Namely, it was found that Water or aqueous solutions in the presence of water-soluble salts containing hydroxyl of aromatic carboxylic acids, considerably larger amounts of o-cresyl-alpha-glycerol ether in take up a clearer solution and, after cooling, try to keep it as pure Water. The shelf life of these solutions is unlimited in closed vessels. Also no crystals separate after standing, however long.
Die genannten Zusatzstoffe werden in Mengen von einigen Prozenten, bezogen auf dieThe mentioned additives are in amounts of a few percent, based on the
fertigenmanufacture
fertigen Lösungen, angewendet, sind für den Körper unschädlich und beeinträchtigen nicht die nmskelerschlaffende Wirkung des Äthers. Am besten hat sich bisher Nstriurasalicylat hierfür bewährt. Die Lösung erfolgt vorzugsweise unter gelindem Erwärmen. Die Beständigkeit der erhaltenen Lösungen spricht dafür, dass Additionsverbindungen entstehen, welche im Körper in ihre Bestandteile zerfallen.finished solutions, applied, are for the Body harmless and do not impair the sleepy effect of the ether. Nstriurasalicylate has proven to be the best for this so far. The solution is preferably done with gentle warming. The stability of the solutions obtained suggests that Addition compounds arise, which break down into their components in the body.
Die nach der Erfindung erhaltenen Lösungen werden zur therapeutischen Verwendung in üblicher ffeise durch Erhitzen sterilisiert und in Akpullen gefüllt,The solutions obtained according to the invention are used in general for therapeutic use five times sterilized by heating and filled in bottles,
1) Io g o-Kresyl-elpha-glycerinäther werden durch Zusatz von 2,5 g Hstriumsalicylat in loo com ?resser bei 4o - 5o° gelöst, «arm. in Ampullen abgefüllt und durch dreimaliges 3o-l*inuten währendes Erhitzen auf 95° aa drei aufeinanderfolgenden Tagen sterilisiert. Diese Lösung ist nach dem Abkühlen in den Ampullen unbegrenzt hsltber.1) Io g o-cresyl-elpha-glycerin ether are made by Addition of 2.5 g of hstrium salicylate in loo com ? resser solved at 4o - 5o °, «poor. filled in ampoules and by heating three times for 30 to 1 minutes while heating to 95 ° aa three successive ones Days sterilized. This solution can be used indefinitely after cooling in the ampoules.
2) 5 g o-Kresyl-elpha-glycerinäther werden mit loo ecm Wasser von 37° aufgeschwemmt und durch Zusatz von 5 g beta-resorcylsaures Natrium zur klaren Lösung gebracht,2) 5 g of o-cresyl-elpha-glycerin ether are added loo ecm of water at 37 ° and by adding 5 g of beta-resorcylic acid sodium to brought a clear solution,
Claims (2)
Family
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