DE1056784B - Process for the preparation of stable injection solutions of 6,8-thioctic acid - Google Patents
Process for the preparation of stable injection solutions of 6,8-thioctic acidInfo
- Publication number
- DE1056784B DE1056784B DEI12984A DEI0012984A DE1056784B DE 1056784 B DE1056784 B DE 1056784B DE I12984 A DEI12984 A DE I12984A DE I0012984 A DEI0012984 A DE I0012984A DE 1056784 B DE1056784 B DE 1056784B
- Authority
- DE
- Germany
- Prior art keywords
- thioctic acid
- solution
- injection solutions
- preparation
- stable injection
- 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
- 239000000243 solution Substances 0.000 title claims description 18
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 title claims description 13
- 238000002347 injection Methods 0.000 title claims description 4
- 239000007924 injection Substances 0.000 title claims description 4
- 238000000034 method Methods 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 229910021529 ammonia Inorganic materials 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- YKLYCOAULSOYSB-UHFFFAOYSA-N phenol;thiourea Chemical compound NC(N)=S.OC1=CC=CC=C1 YKLYCOAULSOYSB-UHFFFAOYSA-N 0.000 claims description 2
- 239000008363 phosphate buffer Substances 0.000 claims description 2
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 235000019136 lipoic acid Nutrition 0.000 description 4
- 229960002663 thioctic acid Drugs 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 239000001488 sodium phosphate Substances 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 241000551546 Minerva Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000001147 anti-toxic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 230000004936 stimulating effect 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
Landscapes
- Health & Medical Sciences (AREA)
- Dermatology (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)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung von stabilen Injektionslösungen der 6,8-Thioctsäure Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von injizierbaren stabilen Lösungen der 6,8-Thioctsäure. Process for the preparation of stable injection solutions of 6,8-thioctic acid The present invention relates to a method of making injectables stable solutions of 6,8-thioctic acid.
Es ist bekannt, daß die 6,8-Thioctsäure pharmakologische Eigenschaften besitzt, die ihre Anwendung in der Therapie als antitoxisches Mittel, als Leberschutz und die Ausscheidungsorgane anregendes Produkt (Colarusso L a r i z z a, Atti del Simposio Internazionale sull' acido tioctico, Napoli, 1955; B on i, Reduzzi, Bile e Gallore, Clin. Terapeut., 9, 129, 1955) bei der Behandlung von Psychosen auf hypodynamischer Grundlage (S erra, Atti del VII Covegno della Societa Italiana di Elettroencefalografia, Padova, Aprile 1956), in der Therapie der Veränderungen des Zuckerhaushalts (L. Pagliaro, Boll. Soc. it. Biol. Sper., 32, 52 [1956]: »Der Einfluß der Thioctsäure auf den Austausch der Kohlenhydrate« sowie »Erste Versuche über den Mechanismus der hypoglycemisierenden Wirkung der Thioctsäure«) und bei Hepatitis in der Paidiatrie (N. Pomponio, Minerva Med., 47, II, 1818 [1956]: »Die Thioctsäure in der Therapie der ansteckenden Hepatis in der Paidiatrie«) gestatten. It is known that 6,8-thioctic acid has pharmacological properties which has its application in therapy as an antitoxic agent, as liver protection and product stimulating the excretory organs (Colarusso L a r i z z a, Atti del Simposio Internazionale sull 'acido tioctico, Napoli, 1955; B on i, Wechszi, Bile e Gallore, Clin. Terapeut., 9, 129, 1955) in the treatment of psychoses on a hypodynamic Basis (Serra, Atti del VII Covegno della Societa Italiana di Elettroencefalografia, Padova, Aprile 1956), in the therapy of changes in the sugar balance (L. Pagliaro, Boll. Soc. it. Biol. Sper., 32, 52 [1956]: »The influence of thioctic acid on the exchange of carbohydrates «and» First attempts on the mechanism the hypoglycemic effect of thioctic acid «) and in hepatitis in paidiatrics (N. Pomponio, Minerva Med., 47, II, 1818 [1956]: “Thioctic acid in therapy infectious hepatis in paidiatrics «).
Die wäßrigen Lösungen der Salze der 6,8-Thioctsäure sind jedoch nicht lagerbeständig. However, the aqueous solutions of the salts of 6,8-thioctic acid are not shelf-stable.
Zweck der vorliegenden Erfindung ist es, diesen Nachteil zu beheben, d. h. stabile, injizierbare Lösungen der 6,8-Thioctsäure herzustellen. The purpose of the present invention is to remedy this disadvantage, d. H. to produce stable, injectable solutions of 6,8-thioctic acid.
Dieses Ziel wird dadurch erreicht, daß man den in Wasser suspendierten Wirkstoff mittels Ammoniak unter Einstellen auf ein pH von 7,7 bis 7,8 in Lösung bringt, die Lösung unter Aufrechterhaltung des pH-Wertes mit einer wäßrigen Thioharnstoff-Phenol-Lösung und einem entsprechenden Phosphatpuffer versetzt, filtriert und unter Stickstoff abfüllt. This goal is achieved by suspending it in water Active ingredient by means of ammonia with adjustment to a pH of 7.7 to 7.8 in solution brings the solution while maintaining the pH value with an aqueous thiourea-phenol solution and a corresponding phosphate buffer are added, filtered and under nitrogen bottling.
Die Erfindung wird nachfolgend in näheren Einzelheiten unter Bezugnahme auf eine praktische Anwendungsform an Hand eines Beispiels beschrieben. The invention is hereinafter referred to in greater detail described on a practical form of application using an example.
Beispiel Herstellung von alterungsbeständigen Injektionslösungen der 6,8-Thioctsäure mit einer Konzentration von 5 mg pro ccm In ein geeignetes Gefäß, das 2 1 destilliertes Wasser enthält, werden 50 g 6,8-Thioctsäure suspendiert, und durch allmähliche Zugabe von konzentriertem Ammoniak (etwa 20 ccm) wird der wirksame Bestandteil in Lösung gebracht. Der p11-Wert der so erhaltenen Lösung muß - mit dem Potentiometer gemessen -im Bereich von 7,7 bis 7,8 liegen. Die Lösung wird weiter mit Wasser bis auf ein Volumen von 5,5 1 ver- dünnt und dann 40 g Phenol und 5 g Thioharnstoff, die vorher gesondert in wenig destilliertem Wasser gelöst wurden, zugegeben. Der pH-Wert wird wiederum kontrolliert und nötigenfalls mit weiterem konzentriertem Ammoniak wieder auf 7,7 und 7,8 eingestellt. Example production of aging-resistant injection solutions of 6,8-thioctic acid at a concentration of 5 mg per ccm in a suitable container, which contains 2 l of distilled water, 50 g of 6,8-thioctic acid are suspended, and by gradually adding concentrated ammonia (about 20 ccm) the effective Component brought into solution. The p11 value of the solution thus obtained must - with Measured with the potentiometer -in the range from 7.7 to 7.8. The solution continues diluted with water up to a volume of 5.5 1 thin and then 40 g of phenol and 5 g Thiourea, which has previously been separately dissolved in a little distilled water, admitted. The pH value is again checked and, if necessary, with more concentrated ammonia readjusted to 7.7 and 7.8.
Gesondert davon werden 476 g Dinatriumphosphat 12 H2 0 und 12,48 g Mononatriumphosphat H2 0 in 3,5 1 destilliertem Wasser gelöst. Die Phosphatlösung wird der vorher - bereiteten Thioctsäurelösung zugegeben und das Volumen mit destilliertem Wasser auf 10 1 aufgefüllt; der pH-Wert wird 7,95 betragen. Die Lösung wird filtriert, in Ampullen gefüllt und unter Stickstoff verschlossen, wobei sie vor Licht geschützt werden.Separately, 476 g of disodium phosphate 12 H2 0 and 12.48 g are used Monosodium phosphate H2 0 dissolved in 3.5 l of distilled water. The phosphate solution is added to the previously prepared thioctic acid solution and the volume with distilled Water made up to 10 1; the pH will be 7.95. The solution is filtered, filled in ampoules and sealed under nitrogen, protecting them from light will.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT1056784X | 1956-05-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1056784B true DE1056784B (en) | 1959-05-06 |
Family
ID=11430002
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEI12984A Pending DE1056784B (en) | 1956-05-24 | 1957-03-19 | Process for the preparation of stable injection solutions of 6,8-thioctic acid |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1056784B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1095991B (en) * | 1959-05-09 | 1960-12-29 | Chemiewerk Homburg Zweignieder | Process for the preparation of a stable and injectable solution containing 1,2-dithia-cyclopentane-3-valeric acid |
| EP0318891A1 (en) * | 1987-12-04 | 1989-06-07 | ASTA Medica Aktiengesellschaft | Injectable solution of thioctic acid containing trometamole and/or basic amino acids |
-
1957
- 1957-03-19 DE DEI12984A patent/DE1056784B/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1095991B (en) * | 1959-05-09 | 1960-12-29 | Chemiewerk Homburg Zweignieder | Process for the preparation of a stable and injectable solution containing 1,2-dithia-cyclopentane-3-valeric acid |
| EP0318891A1 (en) * | 1987-12-04 | 1989-06-07 | ASTA Medica Aktiengesellschaft | Injectable solution of thioctic acid containing trometamole and/or basic amino acids |
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