DE1126069B - Process for the preparation of intravenous injectable, stable aqueous solutions of 2-AEthyl-pyridine-4-carbothionamide - Google Patents
Process for the preparation of intravenous injectable, stable aqueous solutions of 2-AEthyl-pyridine-4-carbothionamideInfo
- Publication number
- DE1126069B DE1126069B DET19061A DET0019061A DE1126069B DE 1126069 B DE1126069 B DE 1126069B DE T19061 A DET19061 A DE T19061A DE T0019061 A DET0019061 A DE T0019061A DE 1126069 B DE1126069 B DE 1126069B
- Authority
- DE
- Germany
- Prior art keywords
- pyridine
- carbothionamide
- aqueous solutions
- preparation
- aethyl
- 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.)
- Pending
Links
- 239000007864 aqueous solution Substances 0.000 title claims description 5
- 238000000034 method Methods 0.000 title claims description 4
- 238000001990 intravenous administration Methods 0.000 title claims 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 15
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 6
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 claims description 3
- RGHNJXZEOKUKBD-SQOUGZDYSA-N Gluconic acid Natural products OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 claims description 3
- 229960005070 ascorbic acid Drugs 0.000 claims description 3
- 235000010323 ascorbic acid Nutrition 0.000 claims description 3
- 239000011668 ascorbic acid Substances 0.000 claims description 3
- 239000000174 gluconic acid Substances 0.000 claims description 3
- 235000012208 gluconic acid Nutrition 0.000 claims description 3
- 159000000003 magnesium salts Chemical class 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 2
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 230000003000 nontoxic effect Effects 0.000 claims 1
- 239000000243 solution Substances 0.000 description 5
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 4
- 229960002001 ethionamide Drugs 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 3
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 3
- 239000001095 magnesium carbonate Substances 0.000 description 3
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 3
- 201000008827 tuberculosis Diseases 0.000 description 3
- 206010028813 Nausea Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000001261 hydroxy acids Chemical class 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (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)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung intravenös injizierbarer, haltbarer wässeriger Lösungen von 2-Athyl-pyridin-4earbothionamid Das 2-Äthyl-pyridin-4-carbothionamid (Ethioniamid) hat sich gegenüber tierexperimenteller und menschlicher Tuberkulose als deutlich wirksam erwiesen (Libermann u. a., Compte Rendu de la Academie des Sciences, 244, S. 402 bis 405, 1957; Bulletin de la Societe de Chimie Biologique, 39, S. 1195 bis 1200, 1957; N. Rist, Atti della Società Lombarda di Scienze Medico-Biologiche, 14, S. 388 bis 394, 1956; Supplementum; Fortschritte der Tuberkuloseforschung, Basel, 10, S. 69 bis 126, 1960). Die perorale klinische Anwendung wird jedoch durch toxische Erscheinungen in Form von Nausea, Erbrechen usw. behindert. Da auch die Absorption des Wirkstoffes nach rektaler Verabfolgung unsicher ist, kommt für die klinische Anwendung noch die parenterale Applikation in Betracht. Die intramuskuläre Injektion einer wäßrigen Suspension von Ethionamid (1 g in 5 ml) ist zwar nach Monod (vgl. Rist, Fortschritte der Tuberkuloseforschung, Basel, 10, S. 69 bis 126, 1960) ohne Nebenwirkungen möglich, wegen der äußerst geringen Löslichkeit des Ethioniamids in Wasser war man bisher jedoch nicht in der Lage, diesen Stoff auch intravenös zu verabfolgen. Process for the preparation of intravenously injectable, durable aqueous Solutions of 2-ethyl-pyridine-4earbothionamide. 2-ethyl-pyridine-4-carbothionamide (Ethioniamide) has been used against animal and human tuberculosis proved to be clearly effective (Libermann et al., Compte Rendu de la Academie des Sciences, 244, pp. 402 to 405, 1957; Bulletin de la Societe de Chimie Biologique, 39, pp. 1195 to 1200, 1957; N. Rist, Atti della Società Lombarda di Scienze Medico-Biologiche, 14, pp. 388 to 394, 1956; Supplement; Progress in tuberculosis research, Basel, 10, pp. 69 to 126, 1960). However, peroral clinical application is rendered toxic by Phenomena in the form of nausea, vomiting, etc. hindered. There is also absorption of the active ingredient is unsafe after rectal administration, comes for the clinical Parenteral application is still being considered. The intramuscular injection An aqueous suspension of ethionamide (1 g in 5 ml) is according to Monod (cf. Rist, progress of tuberculosis research, Basel, 10, pp. 69 to 126, 1960) without Side effects possible because of the extremely low solubility of ethioniamide In water, however, it was previously not possible to use this substance intravenously to be administered.
Im folgenden wird nun ein Verfahren beschrieben, das die Herstellung von haltbaren wäßrigen Lösungen von Ethioniamid mit einem Gehalt bis zu 40/0 ermöglicht. Diese Lösungen haben einen pH-Wert von etwa 5 und sind intravenös injizierbar. In the following, a method will now be described that the production of durable aqueous solutions of ethioniamide with a content of up to 40/0. These solutions have a pH of about 5 and are injectable intravenously.
Erfindungsgemäß können derartige wäßrige Lösungen hergestellt werden, indem man als Lösungsvermittler Citronensäure, Ascorbinsäure und/oder Gluconsäure zusammen mit einem wasserlöslichen Magnesiumsalz verwendet. Das Magnesiumsalz wird dabei in einer Menge bis zu 0,1 g und die Hydroxysäuren in Mengen bis zu 3,2 g, jeweils bezogen auf 1 g Wirkstoff, eingesetzt. According to the invention, such aqueous solutions can be prepared, by using citric acid, ascorbic acid and / or gluconic acid as a solubilizer used together with a water-soluble magnesium salt. The magnesium salt will in an amount up to 0.1 g and the hydroxy acids in amounts up to 3.2 g, in each case based on 1 g of active ingredient, used.
Beispiele 1. In 25 ml Wasser werden 1 g 2-Äthyl-pyridin-4-carbothionamid, 2,5 g Citronensäure und 0,1 g Magnesiumcarbonat in Lösung gebracht. Examples 1. In 25 ml of water, 1 g of 2-ethyl-pyridine-4-carbothionamide, 2.5 g of citric acid and 0.1 g of magnesium carbonate were brought into solution.
2. Iii 25 ml Wasser werden 1 g 2-Äthyl-pyridin-4-carbothionamid, 2,5 g Ascorbinsäure, 0,7 g Citronensäure und 0,1 g Magnesiumcarbonat in Lösung gebracht. 2. III 25 ml of water, 1 g of 2-ethyl-pyridine-4-carbothionamide, 2.5 g of ascorbic acid, 0.7 g of citric acid and 0.1 g of magnesium carbonate were brought into solution.
3. In 25 ml Wasser werden 0,7 g 2-Äthyl-pyridin-4-carbothionamid, 2 g Gluconsäure, 1 g Citronensäure und 0,1 g Magnesiumcarbonat in Lösung gebracht. 3. In 25 ml of water, 0.7 g of 2-ethyl-pyridine-4-carbothionamide, 2 g of gluconic acid, 1 g of citric acid and 0.1 g of magnesium carbonate were brought into solution.
Die bis zu 40/0eigen klaren Lösungen an Wirkstoff zeigen nach 8 Wochen keine Veränderungen. The up to 40/0 clear solutions of active ingredient show up after 8 weeks no changes.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DET19061A DE1126069B (en) | 1960-09-29 | 1960-09-29 | Process for the preparation of intravenous injectable, stable aqueous solutions of 2-AEthyl-pyridine-4-carbothionamide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DET19061A DE1126069B (en) | 1960-09-29 | 1960-09-29 | Process for the preparation of intravenous injectable, stable aqueous solutions of 2-AEthyl-pyridine-4-carbothionamide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1126069B true DE1126069B (en) | 1962-03-22 |
Family
ID=7549181
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DET19061A Pending DE1126069B (en) | 1960-09-29 | 1960-09-29 | Process for the preparation of intravenous injectable, stable aqueous solutions of 2-AEthyl-pyridine-4-carbothionamide |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1126069B (en) |
-
1960
- 1960-09-29 DE DET19061A patent/DE1126069B/en active Pending
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