DE1297103B - Process for the preparation of water-soluble addition compounds of tetracyclines - Google Patents

Process for the preparation of water-soluble addition compounds of tetracyclines

Info

Publication number
DE1297103B
DE1297103B DEM63144A DEM0063144A DE1297103B DE 1297103 B DE1297103 B DE 1297103B DE M63144 A DEM63144 A DE M63144A DE M0063144 A DEM0063144 A DE M0063144A DE 1297103 B DE1297103 B DE 1297103B
Authority
DE
Germany
Prior art keywords
water
tetracyclines
preparation
addition compounds
tetracycline
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
Application number
DEM63144A
Other languages
German (de)
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to DEM63144A priority Critical patent/DE1297103B/en
Publication of DE1297103B publication Critical patent/DE1297103B/en
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/65—Tetracyclines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides

Description

Gegenstand der Erfindung ist ein Verfahren zur Herstellung von wasserlöslichen Additionsverbindungen der Tetracycline mit aromatischen Oxycarbonsäuren in Gegenwart inerter Lösungsmittel, das dadurch gekennzeichnet ist, daß man Tetracyclin . mit einem Methylenaminosalicylat umsetzt. Die hierbei entstehenden Produkte zeichnen sich durch erhöhte bakteriostatische Aktivität und niedrige Toxizität aus. So wurde z. B. festgestellt, daß Natrium - ρ - methylenaminosalicylat - Tetracyclin /einen Wert für die LD™ von 375 mg/kg Maus, Pyrrolidinomethyltetracyclin (»Reverin«) jedoch von 225 mg/kg besitzt.The invention relates to a process for the preparation of water-soluble addition compounds the tetracyclines with aromatic oxycarboxylic acids in the presence of inert solvents, the is characterized in that one tetracycline. with a methylene amino salicylate. the The resulting products are characterized by increased and low bacteriostatic activity Toxicity. So was z. B. found that sodium - ρ - methylenaminosalicylate - tetracycline / a Value for the LD ™ of 375 mg / kg mouse, pyrrolidinomethyltetracycline ("Reverin"), however, possesses 225 mg / kg.

Die Bildung der Anlagerungsverbindung von p-Methylenaminosalicylaten mit Tetracyclin bewirkt, daß die ursprünglich schwer wasserlösliche Substanz nach der Anlagerung leicht wasserlöslich wird.The formation of the addition compound of p-methylene amino salicylates with tetracycline causes that the originally sparingly water-soluble substance becomes readily water-soluble after the attachment.

Beispiel 1
Natrium-p-methylenaminosalicylat-Tetracyclinexample 1
Sodium p-methylene amino salicylate tetracycline

1 g amphoteres Tetracyclin wird unter Rühren in 10 ecm Methylalkohol gelöst. Diese Lösung wird einer Lösung von 0,5 g Na-p-Methylenaminosalicylat in 2 ecm Methylalkohol (ungefähr äquivalente Mengen) zugesetzt. Abscheidung von Na-p-Methylenaminosalicylat-Tetracyclin der Formel1 g of amphoteric tetracycline is dissolved in 10 ecm of methyl alcohol while stirring. This solution will a solution of 0.5 g of Na p-methylene amino salicylate in 2 ecm of methyl alcohol (approximately equivalent amounts) added. Deposition of Na-p-methylene amino salicylate tetracycline the formula

H,CH, C

HO O HOHO O HO

OHOH

erfolgt unmittelbar.takes place immediately.

Das Ganze (Niederschlag und Filtrat) wird im Vakuum zur Trockne eingedampft und das trockene Produkt zur Wiederaufnahme von Kristallwasser 12 Stunden an der Luft stehengelassen. Die Verbindung ist von leuchtendgelber Farbe, löslich in Wasser und in physiologischer Kochsalzlösung. Die Beständigkeit ist von der Konzentration der Na-p-Methylenaminosalicylat - Tetracyclin - Lösung abhängig. Eine hochkonzentrierte Lösung ist 6 bis 8 Stunden beständig. Erhöhung des Prozentgehaltes an p-Methylenaminosalicylat erhöht die Beständigkeit.The whole (precipitate and filtrate) is evaporated to dryness in vacuo and the dry one The product was left to stand in the air for 12 hours in order to reabsorb water of crystallization. The connection is bright yellow in color, soluble in water and in physiological saline solution. The durability depends on the concentration of the Na-p-Methylenaminosalicylat - Tetracycline - solution. A highly concentrated solution is stable for 6 to 8 hours. Increase in the percentage of p-methylene amino salicylate increases durability.

COONaCOONa

OHOH

= CH2 = CH 2

Claims (2)

Patentansprüche:Patent claims: 1. Verfahren zur Herstellung von wasserlöslichen Additionsverbindungen der Tetracycline mit aromatischen Oxycarbonsäuren in Gegenwart inerter Lösungsmittel, dadurch gekennzeichnet, daß man Tetracyclin mit einem p-Methylenaminosalicylat umsetzt.1. Process for the preparation of water-soluble addition compounds of tetracyclines with aromatic oxycarboxylic acids in the presence of inert solvents, characterized in that that one reacts tetracycline with a p-methylene amino salicylate. 2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß man als p-Methylenaminosalicylat das Natrium-p-methylenaminosalicylat verwendet. 2. The method according to claim 1, characterized in that there is used as p-methylene amino salicylate the sodium p-methylene amino salicylate is used.
DEM63144A 1964-11-17 1964-11-17 Process for the preparation of water-soluble addition compounds of tetracyclines Pending DE1297103B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DEM63144A DE1297103B (en) 1964-11-17 1964-11-17 Process for the preparation of water-soluble addition compounds of tetracyclines

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DEM63144A DE1297103B (en) 1964-11-17 1964-11-17 Process for the preparation of water-soluble addition compounds of tetracyclines

Publications (1)

Publication Number Publication Date
DE1297103B true DE1297103B (en) 1969-06-12

Family

ID=7310683

Family Applications (1)

Application Number Title Priority Date Filing Date
DEM63144A Pending DE1297103B (en) 1964-11-17 1964-11-17 Process for the preparation of water-soluble addition compounds of tetracyclines

Country Status (1)

Country Link
DE (1) DE1297103B (en)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE628142A (en) *
DE841146C (en) * 1949-06-15 1952-06-13 Beiersdorf & Co A G P Process for the production of therapeutically valuable condensation products
DE1033657B (en) * 1956-07-07 1958-07-10 Hoechst Ag Process for the preparation of tetracycline salts which are sparingly soluble in water
DE1044806B (en) * 1956-10-03 1958-11-27 Hoechst Ag Process for the preparation of water-soluble derivatives of the tetracyclines
US2880234A (en) * 1954-12-10 1959-03-31 Chase Chemical Company Acid addition products of the tetracyclines
AT205170B (en) * 1958-04-04 1959-09-10 Hoechst Ag Process for the production of salts of the tetracyclines which are sparingly soluble in water
DE1165591B (en) * 1962-02-21 1964-03-19 Merck Ag E Process for the preparation of water-soluble tetracycline derivatives

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE628142A (en) *
DE841146C (en) * 1949-06-15 1952-06-13 Beiersdorf & Co A G P Process for the production of therapeutically valuable condensation products
US2880234A (en) * 1954-12-10 1959-03-31 Chase Chemical Company Acid addition products of the tetracyclines
DE1033657B (en) * 1956-07-07 1958-07-10 Hoechst Ag Process for the preparation of tetracycline salts which are sparingly soluble in water
DE1044806B (en) * 1956-10-03 1958-11-27 Hoechst Ag Process for the preparation of water-soluble derivatives of the tetracyclines
AT205170B (en) * 1958-04-04 1959-09-10 Hoechst Ag Process for the production of salts of the tetracyclines which are sparingly soluble in water
DE1165591B (en) * 1962-02-21 1964-03-19 Merck Ag E Process for the preparation of water-soluble tetracycline derivatives

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