DE3425007A1 - Ambroxol theophylline-7-acetate - Google Patents

Ambroxol theophylline-7-acetate

Info

Publication number
DE3425007A1
DE3425007A1 DE19843425007 DE3425007A DE3425007A1 DE 3425007 A1 DE3425007 A1 DE 3425007A1 DE 19843425007 DE19843425007 DE 19843425007 DE 3425007 A DE3425007 A DE 3425007A DE 3425007 A1 DE3425007 A1 DE 3425007A1
Authority
DE
Germany
Prior art keywords
theophylline
ambroxol
acetate
compound
solvent
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
Application number
DE19843425007
Other languages
German (de)
Other versions
DE3425007C2 (en
Inventor
Giangiacomo Dr. Segrate Mailand/Milano Massaroli
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.)
Poli Industria Chimica SpA
Original Assignee
Poli Industria Chimica SpA
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 Poli Industria Chimica SpA filed Critical Poli Industria Chimica SpA
Publication of DE3425007A1 publication Critical patent/DE3425007A1/en
Application granted granted Critical
Publication of DE3425007C2 publication Critical patent/DE3425007C2/de
Granted legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
    • C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
    • C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
    • C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Ambroxol theophylline-7-acetate of the formula <IMAGE> , the process for its preparation and pharmaceutical compositions containing it are described. The novel salt has expectorant, secretolytic and bronchodilaty activity.

Description

Ambroxol-Theophyllin-7-acetat Ambroxol Theophylline 7 Acetate

Die Erfindung betrifft ein neues Salz des Ambroxols und insbesondere dessen Theophyllin-7-acetat der Formel erhältlich in Form einer kristallinen, weißen Verbindung gut definierter Zusammensetzung, der oben angegebenen Strukturformel vollkommen entsprechend.The invention relates to a new salt of ambroxol and in particular its theophylline-7-acetate of the formula available in the form of a crystalline, white compound of well-defined composition, fully corresponding to the structural formula given above.

Das erfindungsgemäße neue Salz besitzt interessante pharmakologische Eigenschaften. Insbesondere besitzt es neben der auswurfsfördernden und sekretolytischen Aktivität des Ambroxols die bronchodilatorische Aktivität der Theophyllin-7-essigsäure.The new salt according to the invention has interesting pharmacological properties Properties. In particular, it possesses in addition to the expectorant and secretolytic Activity of ambroxol the bronchodilatory activity of theophylline-7-acetic acid.

Das gleichzeitige Vorliegen dieser beiden Aktivitäten macht die erfindungsgemäße Verbindung besonders brauchbar zur Behandlung akuter und chronischer Erkrankungen des Atmungstrakts, die sich durch hypersekretorische und bronchospastische Erscheinungen auszeichnen: Akute und chronische Bronchitis, Bronchialasthma, Lungenemphysem usw..The simultaneous presence of these two activities makes the invention Compound particularly useful for treating acute and chronic diseases of the respiratory tract, which is characterized by hypersecretory and bronchospastic phenomena distinguish: acute and chronic bronchitis, bronchial asthma, emphysema, etc.

Erfindungsgemäß erhält man die Verbindung, indem man äquimolare Mengen der Theophyllin-7-essigsäure und von Ambroxol in aprotischem Lösungsmittel, wie Dimethylformamid, reagieren läßt: Durch Verdünnen der so erhaltenen Lösung mit einem Nicht-Lösungsmittel (z.B. Ethylacetat) erhält man den Niederschlag der erfindungsgemäßen Verbindung, bereits mit ausgezeichnetem Reinheitsgrad.According to the invention, the compound is obtained by adding equimolar amounts of theophylline-7-acetic acid and of ambroxol in aprotic solvent, such as Dimethylformamide, can react: By diluting the resulting solution with a Non-solvents (e.g. ethyl acetate) are used to obtain the precipitate of the invention Compound, already with an excellent degree of purity.

Das folgende Beispiel ist zur Veranschaulichung der Erfindung gegeben, ohne jedwede Beschränkung.The following example is given to illustrate the invention, without any restriction.

Beispiel 238,2 g (1 Mol) Theophyllin-7-essigsäure und 378 g Ambroxol-Base (1 Mol) werden in 2 1 Dimethylformamid bei 400bis zum vollständigen Lösen gerührt. Es wird mit 10 1 Ethylacetat verdünnt, auf 100Cgekühlt, 1 h bei dieser Temperatur gerührt und dann letztlich durch Verdünnen mit 10 1 Ethylacetat die Ausfällung abgeschlossen.Example 238.2 g (1 mole) of theophylline-7-acetic acid and 378 g of ambroxol base (1 mol) are stirred in 2 l of dimethylformamide at 400 to complete dissolution. It is diluted with 10 l of ethyl acetate, cooled to 100 ° C., at this temperature for 1 h stirred and then finally completed the precipitation by dilution with 10 1 ethyl acetate.

Dann wird filtriert, gründlich mit Ethylacetat gewaschen,bei SO°Cunter Vakuum getrocknet, was 525 g (85 %) Ambroxol-Theophyllin-7-acetat mit folgenden Analysenmerkmalen ergibt: Schmp 210 bis 2120r.It is then filtered, washed thoroughly with ethyl acetate, at SO ° C below Vacuum dried, giving 525 g (85%) ambroxol-theophylline-7-acetate with the following Analysis features result in: Melting point 210 to 2120r.

Löslichkeit in Wasser bei 20 C 2,5 z pH einer 1%gen Lösung 5,20+0,2 Ambroxol-Base 61,34%28 Theophyllin-7-essigsäure 38,66%+2% Die Erfindung bezieht sich auch auf alle in Verbindung mit der Anwendunq oder Verwendung der erfindungsgemäßen Verbindung in der Therapie anwendbaren gewerblichen Aspekte.Solubility in water at 20 C 2.5 z pH of a 1% solution 5.20 + 0.2 Ambroxol base 61.34% 28 theophylline-7-acetic acid 38.66% + 2% The invention relates also applies to all in connection with the application or use of the invention Compound in the therapy applicable commercial aspects.

Ein wesentlicher Aspekt der Erfindung liegt daher in pharmazeutischen Zusammensetzungen für orale, parenterale oder inhalatorische Verabreichung, die als wirksames Prinzip die erfindungsgemäße Verbindung neben herkömmlicherweise in der pharmazeutischen Technik verwendeten Exzipientien enthalten.An essential aspect of the invention is therefore pharmaceutical Compositions for oral, parenteral or inhalation administration which as an effective principle, the compound according to the invention in addition to conventionally in contain excipients used in pharmaceutical technology.

Beispiele für solche Zusammensetzungen sind Kapseln, Dragees, Tabletten, Sirup, Tropfen, sterile Ampullen für Injektionen und Aerosol usw..Examples of such compositions are capsules, coated tablets, tablets, Syrup, drops, sterile ampoules for injections and aerosol, etc.

Claims (1)

Patentansprüche 1. Ambroxol-Theophyllin-7-acetat der Formel 2. Verfahren zur Herstellung der Verbindung gemäß Anspruch 1, dadurch gekennzeichnet, daß man äquimolare Mengen von Theophyllin-7-essigsäure und Ambroxol-Base in aprotischem Lösungsmittel reagieren läßt und die so erhaltene Verbindung durch Ausfällen mit einem Nicht-Lösungsmittel isoliert.Claims 1. Ambroxol-Theophylline-7-acetate of the formula 2. Process for the preparation of the compound according to claim 1, characterized in that equimolar amounts of theophylline-7-acetic acid and ambroxol base are allowed to react in an aprotic solvent and the compound thus obtained is isolated by precipitation with a non-solvent. 3. Verfahren nach Anspruch 2, dadurch gekennzeichnet, daß man in Dimethylformamid arbeitet. 3. The method according to claim 2, characterized in that in Dimethylformamide works. 4. Verfahren nach Anspruch 2, dadurch gekennzeichnet, daß man als Nicht-Lösungsmittel Ethylacetat verwendet. 4. The method according to claim 2, characterized in that as Non-solvent ethyl acetate used. 5. Pharmazeutische Zusammensetzung, enthaltend als wirksames Prinzip das Ambroxol-Theophyllin-7-acetat gemäß Anspruch 1. 5. Pharmaceutical composition containing as an effective principle the ambroxol-theophylline-7-acetate according to claim 1. 6. Zusammensetzung nach Anspruch 5 in Form von Kapseln, Tabletten, Sirup, Ampullen für intravenöse, intramuskuläre Injektion oder Aerosol. 6. Composition according to claim 5 in the form of capsules, tablets, Syrup, ampoules for intravenous, intramuscular injection or aerosol.
DE19843425007 1983-07-06 1984-07-06 Ambroxol theophylline-7-acetate Granted DE3425007A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
IT21953/83A IT1165457B (en) 1983-07-06 1983-07-06 TEOFILLIN-7-AMBROXOL ACETATE

Publications (2)

Publication Number Publication Date
DE3425007A1 true DE3425007A1 (en) 1985-01-17
DE3425007C2 DE3425007C2 (en) 1990-11-15

Family

ID=11189330

Family Applications (1)

Application Number Title Priority Date Filing Date
DE19843425007 Granted DE3425007A1 (en) 1983-07-06 1984-07-06 Ambroxol theophylline-7-acetate

Country Status (3)

Country Link
DE (1) DE3425007A1 (en)
ES (1) ES534035A0 (en)
IT (1) IT1165457B (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3530761A1 (en) * 1985-08-28 1987-03-05 Klinge Co Chem Pharm Fab Pharmaceutical combination having synergistic action
DE3610997A1 (en) * 1986-04-02 1987-10-15 Krewel Werke Gmbh AMBROXOL NOSE SPRAY
EP0274106A2 (en) * 1987-01-07 1988-07-13 ERREGIERRE INDUSTRIA CHIMICA Spa N-(trans-p-hydroxy-cyclohexyl)-(2-amino-3,5-dibromo)benzylamine salts possessing mucolytic activity

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
NICHTS ERMITTELT *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3530761A1 (en) * 1985-08-28 1987-03-05 Klinge Co Chem Pharm Fab Pharmaceutical combination having synergistic action
DE3610997A1 (en) * 1986-04-02 1987-10-15 Krewel Werke Gmbh AMBROXOL NOSE SPRAY
EP0274106A2 (en) * 1987-01-07 1988-07-13 ERREGIERRE INDUSTRIA CHIMICA Spa N-(trans-p-hydroxy-cyclohexyl)-(2-amino-3,5-dibromo)benzylamine salts possessing mucolytic activity
US4845114A (en) * 1987-01-07 1989-07-04 Erregierre Industria Chimica Spa N-(trans-p-hydroxy-cyclohexyl)-(2-amino-3,5-dibromo)benzylamine salts possessing mucolytic activity
EP0274106A3 (en) * 1987-01-07 1989-11-08 ERREGIERRE INDUSTRIA CHIMICA Spa N-(trans-p-hydroxy-cyclohexyl)-(2-amino-3,5-dibromo)benzylamine salts possessing mucolytic activity

Also Published As

Publication number Publication date
ES8506710A1 (en) 1985-08-01
ES534035A0 (en) 1985-08-01
DE3425007C2 (en) 1990-11-15
IT8321953A0 (en) 1983-07-06
IT1165457B (en) 1987-04-22

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8110 Request for examination paragraph 44
D2 Grant after examination
8364 No opposition during term of opposition
8339 Ceased/non-payment of the annual fee