DEF0017503MA - - Google Patents
Info
- Publication number
- DEF0017503MA DEF0017503MA DEF0017503MA DE F0017503M A DEF0017503M A DE F0017503MA DE F0017503M A DEF0017503M A DE F0017503MA
- Authority
- DE
- Germany
- Prior art keywords
- salts
- sarcosine anhydride
- pas
- sarcosine
- ecm
- 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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- 239000011780 sodium chloride Substances 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 9
- GPAYXCOQADGNAZ-UHFFFAOYSA-N [2-(methylamino)acetyl] 2-(methylamino)acetate Chemical compound CNCC(=O)OC(=O)CNC GPAYXCOQADGNAZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 6
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-Aminosalicylic acid Chemical class NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 230000000087 stabilizing Effects 0.000 claims description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N Salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims 1
- -1 Salts sarcosine anhydride Chemical class 0.000 claims 1
- 239000003381 stabilizer Substances 0.000 claims 1
- CWLKGDAVCFYWJK-UHFFFAOYSA-N 3-Aminophenol Chemical compound NC1=CC=CC(O)=C1 CWLKGDAVCFYWJK-UHFFFAOYSA-N 0.000 description 4
- 229940018563 3-aminophenol Drugs 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000003638 reducing agent Substances 0.000 description 2
- TUDXHDSCPJSDIO-UHFFFAOYSA-N 4-amino-2-hydroxybenzoic acid;sodium Chemical compound [Na].NC1=CC=C(C(O)=O)C(O)=C1 TUDXHDSCPJSDIO-UHFFFAOYSA-N 0.000 description 1
- 229940043230 Sarcosine Drugs 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Substances O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 238000005755 formation reaction Methods 0.000 description 1
- KLGZELKXQMTEMM-UHFFFAOYSA-N hydride Chemical compound [H-] KLGZELKXQMTEMM-UHFFFAOYSA-N 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine zwitterion Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- VYGBQXDNOUHIBZ-UHFFFAOYSA-L sodium formaldehyde sulphoxylate Chemical compound [Na+].[Na+].O=C.[O-]S[O-] VYGBQXDNOUHIBZ-UHFFFAOYSA-L 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000002588 toxic Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
Description
BUNDESREPUBLIK DEUTSCHLANDFEDERAL REPUBLIC OF GERMANY
Tag der Anmeldung: 11. Mai 1955 Bekanntgemacht am 22, November 1956Date of registration: May 11, 1955 Advertised on November 22, 1956
DEUTSCHES PATENTAMTGERMAN PATENT OFFICE
p-Aminosalieylsäure (PAS) wird in großem Ausmaß als wäßrige Lösung ihrer Salze, vor allem ihres Natriumsalzes, zur Behandlung verschiedener Formen der Tuberculose eingesetzt. Die Lösungen sind nur sehr kurze Zeit haltbar. Es. entsteht neben anderen, braungefärbten Zersetzung^- bzw. Oxydationsprodukten' das wegen seiner Toxizität höchst unerwünschte PAS-Dekarboxylierungsprodukt m-Aminophenol.p-Aminosalicic acid (PAS) is used in large quantities Extent as an aqueous solution of their salts, especially their sodium salt, for the treatment of various Forms of tuberculosis used. The solutions can only be kept for a very short time. It. arises next to other, brown-colored decomposition ^ - or oxidation products' because of its toxicity highly undesirable PAS decarboxylation product m-aminophenol.
Es ist bekannt, wäßrigen Lösungen von p-aminosalicylsaurem Natrium zum Zwecke der Stabilisierung ο,οΐ bis 2 Gewichtsprozent Formaldehydsulfoxylatnatrium zuzusetzen. Hierdurch wird das Auftreten braungefärbter Oxydationsprodukte hintangehalten. Die Erfahrung hat aber gelehrt, daß die Intensität der Verfärbung von wäßrigen Lösungen p-aminosalicylsaurer Salze keinesfalls ein Gradmesser für die durch Abspaltung von Kohlendioxyd erfolgende Zersetzung ist. Durch Zusatz von Reduktionsmitteln wie Formaldehydsulf oxy latnatrium farblos gehaltene wäßrige Lösungen p-aminos'alicylsaurer Salze können sogar wesentlich höheren m-Aminophenolgehalt haben, also erheblich toxischer sein, als mehr oder weniger verfärbte Lösungen, die kein Reduktionsmittel enthalten.It is known to use aqueous solutions of p-aminosalicylic acid Sodium for the purpose of stabilization ο, οΐ to 2 percent by weight formaldehyde sulfoxylate sodium to add. This prevents the occurrence of brown-colored oxidation products. But experience has taught that the intensity of the discoloration of aqueous solutions of p-aminosalicylic acid salts by no means is a yardstick for the decomposition that takes place through the splitting off of carbon dioxide. Through Addition of reducing agents such as formaldehyde sulf oxy latnatrium colorless aqueous solutions p-aminos'alicylic acid salts can even be essential have a higher m-aminophenol content, i.e. be considerably more toxic than more or less discolored solutions that do not contain a reducing agent.
609 708/334609 708/334
F 17503 IVa/30hF 17503 IVa / 30h
Es wurde nun gefunden, daß Sarkosinanhydrid PAS-Salze zu stabilisieren vermag. Sarkosinanhydrid enthaltende Lösungen von PAS-Salzen verfärben sich nicht nur erheblich langsamer, sondern sind, was für die Praxis' noch bedeutsamer ist, hinsichtlich des Entstehens von m-Aminophenol bemerkenswert stabil. Sarkosinanhydrid zeichnet sich durch gute physiologische Verträglichkeit aus. Die stabilisierende Wirkung des Sarkosinanhydrids erstreckt sich nicht nur auf anorganische Salze der PAS, sondern auch auf Salze dieser Säure mit organischen Basen. Das Sarkosinanhydrid kann den wäßrigen Lösungen der PAS-Salze zugesetzt bzw. zusammen mit diesen gelöst werden. Es- kann aber auch mit den PAS-Salzen in Trockenmiscbunr gen übergeführt werden, die, gegebenenfalls in Ampullen od. dgl. abgefüllt, im Bedarfsfalle gelöst werden.It has now been found that sarcosine anhydride is able to stabilize PAS salts. Sarcosine anhydride containing solutions of PAS salts not only discolor much more slowly, but are, which is even more important in practice, with regard to the formation of m-aminophenol remarkably stable. Sarcosine anhydride is characterized by good physiological tolerance. The stabilizing effect of the sarcosine anhydride does not only extend to the inorganic salts PAS, but also to salts of this acid with organic bases. The sarcosine anhydride can added to the aqueous solutions of the PAS salts or dissolved together with them. It can but also with the PAS salts in a dry mix gene are transferred, which, if necessary or in ampoules. The like. Filled, if necessary, dissolved will.
Unter aseptischen Bedingungen hergestellte und in Ampullen abgefüllte wäßrige sterile Lösungen (10 Gew./Vol.°/o) von Natrium-p-aminosalicylai ■ 2H2O enthielten nach 2monatiger Lagerung folgende Mengen von m-Aminophenol: Aqueous sterile solutions (10 w / v) of sodium p-aminosalicylai ■ 2H 2 O after 2 months of storage contained the following amounts of m-aminophenol, prepared under aseptic conditions and filled into ampoules:
ohne Sarkosinariihydridzüsatz . ., . 84 mg/100 ecm' mit Zusatz vonwithout sarcosine hydride addition. .,. 84 mg / 100 ecm ' with the addition of
5°/o Sarkosinanhydrid .65 mg/100 ecm5% sarcosine anhydride, 65 mg / 100 ecm
10% - 40 mg/100 ecm10% - 40 mg / 100 ecm
°/o - 26 mg/100 ecm° / o - 26 mg / 100 ecm
20% - ...'.· 19 mg/100 ecm20% - ... '. 19 mg / 100 ecm
2.5 °/o - 12 mg/100 ecm2.5% - 12 mg / 100 ecm
Claims (3)
Britische Patentschrift Nr. 700 774.Considered publications:
British Patent No. 700 774.
Family
ID=
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