DE2013267B2 - Vitamin B deep 1-disulfide-di-nicotinate - Google Patents
Vitamin B deep 1-disulfide-di-nicotinateInfo
- Publication number
- DE2013267B2 DE2013267B2 DE19702013267 DE2013267A DE2013267B2 DE 2013267 B2 DE2013267 B2 DE 2013267B2 DE 19702013267 DE19702013267 DE 19702013267 DE 2013267 A DE2013267 A DE 2013267A DE 2013267 B2 DE2013267 B2 DE 2013267B2
- Authority
- DE
- Germany
- Prior art keywords
- disulfide
- vitamin
- thiamine disulfide
- dinicotinate
- thiamine
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
Description
c=c'c = c '
I \I \
CH3 CH2-CH2-OHCH 3 CH 2 -CH 2 -OH
COOHCOOH
2. Verfahren zur Herstellung des Dinicotinates des Thiamindisulfids gemäß Anspruch 1, dadurch gekennzeichnet, daß in an sich bekannter Weise Thiamindisulfid mit Nicotinsäure in molaren Verhaltnissen umgesetzt wird.2. Process for the preparation of the dinicotinate of thiamine disulfide according to claim 1, characterized in that that in a known manner thiamine disulfide with nicotinic acid in molar proportions is implemented.
3. Arzneimittel, bestehend aus dem Dinicotinat des Thiamindisulfids nach Anspruch 1 und üblichen Hilfs- und Trägerstoffen.3. Medicaments consisting of the dinicotinate of thiamine disulfide according to claim 1 and usual Auxiliary and carrier materials.
Die Erfindung betrifft das Dinicotinat des Thiamindisulfids der nachstehenden Konstitution
N—C—NH, CHOThe invention relates to the dinicotinate of thiamine disulfide of the following constitution
N — C — NH, CHO
Ii Il /Ii Il /
CH3-C C-CH2-N S—CH 3 -C C-CH 2 -NS-
N=CH C=CN = CH C = C
CH3 CH 3
CH2 CH2 OHCH 2 CH 2 OH
· 2· 2
COOHCOOH
Verfahren zu dessen Herstellung und Arzneimittel, bestehend aus dieser Verbindung und üblichen Hilfsund Trägerstoffen.Process for its production and medicament, consisting of this compound and customary auxiliaries Carriers.
Es wurde gefunden, daß dieses Dinicotinat des Thiamindisulfids in an sich bekannter Weise durch Umsetzung von Thiamindisulfid mit Nicotinsäure in molaren Verhältnissen, gegebenenfalls in einem Lösungs- und Verdünnungsmittel, wie Alkoholen oder Wasser, bei gewöhnlicher oder erhöhter Temperatur erhalten wird. Das Thiamindisulfiddinicotinat bildet farblose Kristalle, die in Wasser leicht löslich sind und auch einen verminderten bitteren Geschmack gegenüber dem Ausgangsprodukt ergeben. Es ist wesentlich ungiftiger als Thiamindisulfid, ergibt hohe Blutspiegelwerte an Vitamin Bx, zeigt sich verstärkt bei Avitaminosen wirksam, potenziert die therapeutische Wirkung der Analgetika und von sedativ wirksamen Körpern und ergibt eine ausgezeichnete Wirkung bei experimentell erzeugten Leberverfettungen.It has been found that this dinicotinate of thiamine disulfide is obtained in a manner known per se by reacting thiamine disulfide with nicotinic acid in molar proportions, optionally in a solvent and diluent, such as alcohols or water, at normal or elevated temperature. The thiamine disulfide dinicotinate forms colorless crystals that are easily soluble in water and also result in a reduced bitter taste compared to the starting product. It is significantly less toxic than thiamine disulfide, results in high blood levels of vitamin B x , is more effective in avitaminoses, potentiates the therapeutic effect of analgesics and sedative bodies and has an excellent effect on experimentally produced fatty liver.
Es wurden zunächst die Toxizitätsdaten gegenüber den bekannten Vitamin-B,-Derivaten gezeigt. Die Bestimmung der DL50 erfolgte nach K ä r b e r an weißen Mäusen in mg/kg.First of all, the toxicity data for the known vitamin B, derivatives were shown. The DL 50 was determined according to Kärber on white mice in mg / kg.
Das erfindungsgemäße Dinicotinat des Thiamindisulfids ist also wesentlich weniger giftig als bekannte Vergleichssubstanzen. Die Gegenüberstellung der erhaltenen Blutspiegelwerte erfolgt in der nachstehenden Tabelle. Von jeder Substanz wurden 10 -mg-Äquivalente Vitamin-B,-Hydrochlorid oral an Hauskaninchen pro 3 kg Durchschnittskörpergewicht verabreicht und die Blut-Thiaminspiegel ( %) festgehalten. The dinicotinate of thiamine disulfide according to the invention is therefore significantly less toxic than known ones Comparison substances. The comparison of the blood level values obtained is shown below Tabel. 10 mg equivalents of vitamin B, hydrochloride of each substance were administered orally to domestic rabbits administered per 3 kg of average body weight and the blood thiamine level (%) recorded.
Substanzsubstance
Vitamin-B,-Hydrochlorid Vitamin B, hydrochloride
Thiamindisulfid .
O,O'-Dibenzoyl-Thiamine disulfide.
O, O'-dibenzoyl-
thiamindisulfid ,
Thiamindisulfiddinicotinat thiamine disulfide,
Thiamine disulfide dinicotinate
nach Stundenafter hours
13,0
26,513.0
26.5
56,0
45,556.0
45.5
Substanz.Substance.
Vitamin-B^Hydrochlorid Vitamin B ^ hydrochloride
Thiamindisulfid ...Thiamine disulfide ...
O,O'-Dibenzoylthiamindisulfid ..O, O'-dibenzoylthiamine disulfide ..
Thiamindisulfiddinicotinat Thiamine disulfide dinicotinate
oralorally
6000 70006000 7000
7500 9000 Die erhaltenen Blutspiegelwerte sind somit dem Vitamin-B,-Hydrochlorid weit überlegen, sind günstiger als gegenüber dem Thiamindisulfid selbst und nur wenig niedriger als die mit O,O'-Dibenzoylthiamindisulfid, also einem Thiamin disulfid-esler, erreichbaren. Sie sind somit für ein Vitamin-B,-Salz überraschend hoch.7500 9000 The blood level values obtained are therefore far superior to vitamin B, hydrochloride, and are cheaper than compared to the thiamine disulfide itself and only slightly lower than that with O, O'-dibenzoylthiamine disulfide, So a thiamine disulfide donor, achievable. You are therefore in favor of a vitamin B salt surprisingly high.
Die antagonistische Wirkung gegenüber der durch Tetrachlorkohlenstoff hervorgerufenen Leberverfettung wurde an weiblichen Wistarratten durch den Einfluß auf die durch Tetrachlorkohlenstoff bedingte Verlängerung der Schlafdauer geprüft (Versuchsanordnung nach D. Lemke , Acta biol. med. The antagonistic effect on the fatty liver caused by carbon tetrachloride was found in female Wistar rats by the influence on carbon tetrachloride Extension of sleep duration tested (test arrangement according to D. Lemke, Acta biol. Med.
germ. 3, 37 [1959]). Die Behandlung wurde mit den geprüften Substanzen in Dosen von 100 mg 4 Tage lang peroral ausgeführt. Am zweiten Behandlungstag wurde Tetrachlorkohlenstoff gegeben. Die Ergebnisse sind in der nachfolgenden Tabelle angegeben.germ. 3, 37 [1959]). The treatment was carried out with the tested substances in doses of 100 mg for 4 days long performed orally. Carbon tetrachloride was given on the second day of treatment. The results are given in the table below.
KontrollenControls
Tetrachlorkohlenstoff TiereCarbon tetrachloride animals
Vitamin-B,-Hvdröchlorid Vitamin-B, -Hvdrochlorid
ThiamindisulfidThiamine disulfide
Thiamindisulfiddinicotinul Thiamine disulfide dinicotinul
Schlafdauer in
Minuten ...Sleep duration in
Minutes ...
Zahl der Tiere ..Number of animals ..
28,5 _ 1,8
1528.5 _ 1.8
15th
64,5 _ 3,5
1564.5-3.5
15th
65,4 _ 3,2
1665.4-3.2
16
64,8 _ 3,5
1664.8-3.5
16
38,3 _ 3,2
1638.3-3.2
16
Das Dinioolinat des Thiamindisulfids hat also einen eindeutigen Einfluß auf die durch Tetrachlorkohlenstoff bedingte Leberverfettung.The dinioolinate of thiamine disulfide has a clear influence on the fatty liver caused by carbon tetrachloride.
Das Dinicotinat des Thiamindisulfids hat also neben einer guten VItHmIn-B1-Wirksamkeit eine beachtliche Leberschutzwirkung und dient in Form von Tabletten, Dragees, Pulvern oder anderen konventionellen Zubereitungsformen als Arzneimittel.The dinicotinate of thiamine disulfide thus has not only a good VItHmIn-B 1 effectiveness but also a considerable protective effect on the liver and is used as a medicament in the form of tablets, coated tablets, powders or other conventional preparation forms.
Die folgenden Beispiele erläutern die Herstellung der erfindungsgemäßen Verbindung:The following examples illustrate the preparation of the compound according to the invention:
28,6 g Thiamindisulfid werden in etwa 100 ml Methanol suspendiert. Dazu werden 12 g Nicotinsäure zugesetzt und alles 30 Minuten auf dem Wasserbade erwärmt. Es tritt Auflösung ein, und alsbald fällt das Nicotinat bereits während der Erwärmung aus. Man läßt erkalten, verdünnt zur Vervollständigung der Auskristallisation mit Äther, läßt 24 bis 30 Stunden stehen, saugt die Kristalle ab und wäscht mit Äther nach. Ausbeute etwa 39 g.28.6 g of thiamine disulfide are suspended in about 100 ml of methanol. To do this, 12 g of nicotinic acid are added added and everything was heated on the water bath for 30 minutes. There is dissolution, and immediately the nicotinate precipitates during the warming up. Allow to cool, dilute to complete crystallization with ether, left to stand for 24 to 30 hours, sucks the crystals off and washes with ether after. Yield about 39 g.
Fp.: Sintert bei HO0C, schmilzt bei 158 bis 1600C orangegefärbt.Fp .: sintered at HO 0 C, melts at 158 to 160 0 C, colored orange.
28,6 g Thiamindisulfid und 12 g Nicotinsäure werden in etwa 60 ml warmem Wasser gelöst. Die Lösung wird alsdann im Vakuum eingedampft. Es werden 38 g farblose Kristalle erhalten, die durch Umkristailisation aus 80%igem Methanol gereinigt werden können.28.6 g of thiamine disulfide and 12 g of nicotinic acid are dissolved in about 60 ml of warm water. The solution is then evaporated in vacuo. There are 38 g of colorless crystals obtained by recrystallization can be purified from 80% methanol.
Fp.: Sintert bei HO0C, schmilzt bei 158 bis 16O0C mit Orange-Farbe.Fp .: sintered at HO 0 C, melts at 158 to 16O 0 C with an orange color.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19702013267 DE2013267C3 (en) | 1970-03-20 | 1970-03-20 | Vitamin B deep 1-disulfide-di-nicotinate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19702013267 DE2013267C3 (en) | 1970-03-20 | 1970-03-20 | Vitamin B deep 1-disulfide-di-nicotinate |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE2013267A1 DE2013267A1 (en) | 1971-10-07 |
| DE2013267B2 true DE2013267B2 (en) | 1974-06-27 |
| DE2013267C3 DE2013267C3 (en) | 1975-02-20 |
Family
ID=5765649
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19702013267 Expired DE2013267C3 (en) | 1970-03-20 | 1970-03-20 | Vitamin B deep 1-disulfide-di-nicotinate |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE2013267C3 (en) |
-
1970
- 1970-03-20 DE DE19702013267 patent/DE2013267C3/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| DE2013267A1 (en) | 1971-10-07 |
| DE2013267C3 (en) | 1975-02-20 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C3 | Grant after two publication steps (3rd publication) | ||
| E77 | Valid patent as to the heymanns-index 1977 | ||
| 8339 | Ceased/non-payment of the annual fee |