DE3427787A1 - ACTIVE SUBSTANCE COMPLEXES OF 5-METHOXY-2 ((4-METHOXY-3,5-DIMETHYL-2-PYRIDYL) METHYLSULFINYL) -1H-BENZIMIDAZOLE WITH CYCLODEXTRINES, THEIR PRODUCTION AND MEDICINAL PRODUCTS - Google Patents
ACTIVE SUBSTANCE COMPLEXES OF 5-METHOXY-2 ((4-METHOXY-3,5-DIMETHYL-2-PYRIDYL) METHYLSULFINYL) -1H-BENZIMIDAZOLE WITH CYCLODEXTRINES, THEIR PRODUCTION AND MEDICINAL PRODUCTSInfo
- Publication number
- DE3427787A1 DE3427787A1 DE19843427787 DE3427787A DE3427787A1 DE 3427787 A1 DE3427787 A1 DE 3427787A1 DE 19843427787 DE19843427787 DE 19843427787 DE 3427787 A DE3427787 A DE 3427787A DE 3427787 A1 DE3427787 A1 DE 3427787A1
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- methoxy
- benzimidazole
- inclusion complexes
- dimethyl
- cyclodextrines
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
- C08B37/0012—Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
- C08B37/0015—Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes
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- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Nanotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
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- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
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- Crystallography & Structural Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Medical Informatics (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Wirkstoffkomplexe von 5-Methoxy-2-(4-methoxy-3,5- Active ingredient complexes of 5-methoxy-2- (4-methoxy-3,5-
dimethyl-2-pyridyl)methylsulfinyl]-1H-benzimidazol mit Cvclodextrinen. deren Herstellung und Arzneimittel WirkstoffkomDlexe von 5-Hethoxv-2-( (&-methoxv-3 .5-dimethvl-2-Dvridvllmethvlsulfinvll-lH-benzimidazol mit Cvclodextrinen. deren Herstelluna und Arzneimittel Die Erfindung betrifft neue Cyclodextrin-Einschlußverbindungen, Verfahren zu ihrer Herstellung, ihre Anwendung und sie enthaltende Arzneimittel. Die erfindungsgem08en Verbindungen werden als pharmakologisch wirksame Stoffe in Arzneimitteln eingesetzt. dimethyl-2-pyridyl) methylsulfinyl] -1H-benzimidazole with clodextrins. their manufacture and pharmaceuticals Active ingredient complexes of 5-Hethoxv-2- ( (& -methoxv-3 .5-dimethvl-2-Dvridvllmethvlsulfinvll-1H-benzimidazole with Cvclodextrinen. their manufacture and pharmaceuticals The invention relates to new cyclodextrin inclusion compounds, Process for their production, their use and pharmaceuticals containing them. The compounds according to the invention are used as pharmacologically active substances in Medicines used.
Stand der Technik Es ist bekannt, daß Cyclodextrine mit bestimmten pharmazeutischen Wirkstoffen Einschlußverbindungen bilden können (z.B. EP-A-56 995, DE-A-32 26 232, DE-A-30 15 626, EP-A-91 782, DE-A-31 18 218 und EP-A-72 868). Weiterhin sind aus der europaischen Patentanmeldung EP-A-5 129 Benzimidazolderivate bekannt, die wertvolle pharmakologische Eigenschaften besitzen. Aus der europäischen Patentanmeldung EP-A-103 553 ist weiterhin bekannt, daß sich die Benzimidazolderivate der EP-A-5 129 tz.B. der Wirkstoff Omeprazol (INN) =5-Methoxy-2-((&-methoxy-3 .5-dimethyl-2-pyridyl)methylsulfinyl3-1H-benzimidazol) schneller als erwünscht zersetzen.Background Art It is known that cyclodextrins with certain pharmaceutical active ingredients can form inclusion compounds (e.g. EP-A-56 995, DE-A-32 26 232, DE-A-30 15 626, EP-A-91 782, DE-A-31 18 218 and EP-A-72 868). Farther are known from the European patent application EP-A-5 129 benzimidazole derivatives, which have valuable pharmacological properties. From the European patent application EP-A-103 553 is also known that the benzimidazole derivatives of EP-A-5 129 e.g. the active ingredient omeprazole (INN) = 5-methoxy-2 - ((& - methoxy-3 .5-dimethyl-2-pyridyl) methylsulfinyl3-1H-benzimidazole) decompose faster than desired.
Beschreibung der Erfindung Oberraschenderweise wurde nun gefunden, daß sich ausgehend von den in der EP-A-5 129 genannten Verbindungen (insbesondere ausgehend von Omeprazol) mit Cyclodextrinen EinschluBverbindungen (:Inklusionskomplexe) herstellen lassen, die sich durch eine hohe Stabilitat auszeichnen.Description of the invention Surprisingly, it has now been found that based on the compounds mentioned in EP-A-5 129 (in particular starting from omeprazole) with cyclodextrins inclusion compounds (: inclusion complexes) can be produced, which are characterized by a high stability.
Gegenstand der Erfindung sind daher neue Inklusionskomplexe von Omeprazol mit Cyclodextrinen.The invention therefore relates to new inclusion complexes of omeprazole with cyclodextrins.
Als Cyclodextrine eignen sich unsubstituierte Cyclodextrine wie z.B.Unsubstituted cyclodextrins such as e.g.
o-, B- und y-Cyclodextrin, oder substituierte {z.B. partiell methylierte) Cyclodextrine, wie z.B. Heptakis-(3-O-methyl)-ß-cyclodextrin oder Heptakis-(2,6-di-0-methyl)-B-cyclodextrin, wobei die Cyclodextrine gemischt oder in reiner Form vorliegen können. Bevorzugt ist das ß-Cyclodextrin.o-, B- and γ-cyclodextrin, or substituted {e.g. partially methylated) Cyclodextrins, such as heptakis- (3-O-methyl) -ß-cyclodextrin or heptakis- (2,6-di-0-methyl) -B-cyclodextrin, it being possible for the cyclodextrins to be mixed or in pure form. Preferred is the ß-cyclodextrin.
Das molare Verhältnis Cyclodextrin:Omeprazol kann in einem breiten Bereich, beispielsweise von 10:1 bis 1:10 variieren, wobei ein Verhältnis Cyclodextrin:Omeprazol von 1:i (z.B. von 1:1 bis 5:1) bevorzugt ist da sich nur so der gewunschte Stabilisierungseffekt voll einstellen kann.The molar ratio of cyclodextrin: omeprazole can be varied in a wide range Range, for example, from 10: 1 to 1:10, with a cyclodextrin: omeprazole ratio from 1: i (e.g. from 1: 1 to 5: 1) is preferred as this is the only way to achieve the desired stabilizing effect can fully adjust.
Weiterer Gegenstand der Erfindung ist ein Verfahren zur Herstellung der erfindungsgemäßen Inklusionskomplexe. Das Verfahren ist dadurch gekennzeichnet, daB man Omeprazol in einem geeigneten Lösungsmittel mit Cyclodextrin umsetzt.The invention also relates to a method for production the inclusion complexes according to the invention. The procedure is characterized by that omeprazole is reacted with cyclodextrin in a suitable solvent.
Welche Lösungsmittel bevorzugt sind ist dem Fachmann aufgrund seines Fachwissens geläufig. So konnen wasserhaltige oder wasserfreie Lösungsmittel eingesetzt werden, wobei Lösungsmittel mit nicht allzuhohem Wasseranteil bevorzugt sind. Beispielsweise seien Alkohole, wie Methanol, Isopropanol oder insbesondere Ethanol genannt.Which solvents are preferred is a person skilled in the art because of his Knowledgeable. Thus, aqueous or anhydrous solvents can be used Solvents with a not too high water content are preferred. For example alcohols such as methanol, isopropanol or, in particular, ethanol may be mentioned.
Die Reaktionstemperatur des erfindungsgemäßen Verfahrens kann innerhalb gewisser Grenzen schwanken, wobei Temperaturen zwischen 25 und 380C, insbesondere Temperaturen zwischen 30 und 340 bevorzugt sind. Es konnen natürlich auch höhere oder tiefere Temperaturen zur Anwendung kommen wobei jedoch gegebenenfalls Ausbeuteverluste in Kauf genommen werden müssen. Insbesondere bei der Anwendung höherer Temperaturen sollte ein langsames Abkühlen erfolgen.The reaction temperature of the process according to the invention can be within fluctuate within certain limits, with temperatures between 25 and 380C, in particular Temperatures between 30 and 340 are preferred. It can of course also be higher or lower temperatures are used, however, yield losses may occur must be accepted. Especially when using higher temperatures should be allowed to cool slowly.
Das folgende Beispiel erläutert die Erfindung näher ohne sie einzuschränken. Für Stunde(n) wird die Abkürzung h verwendet.The following example explains the invention in more detail without restricting it. The abbreviation h is used for hour (s).
Beispiel ß-Cvclodextrin-Einschlußverbindung mit 5-Methoxy-2[(4-methoxy-3,5-dimethyl-2-pyridylmethyl)sulfinyl]-(1H)-benzimidazol 1,73 g 5-Methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridylmethyl)sulfinyl)-(1H)-benzimidazol (5mMol) und 5,67 g ß-Cyclodextrin werden mit 20 ml 96%igem Ethanol versetzt und das Gemisch 15 h bei 30-320C Innentemperatur kräftig gerührt. Danach kühlt man innerhalb von 3 h auf 100C ab, gießt über ein Filter und wäscht grundlich mit 100C kaltem Ethanol nach. Nach Trocknung im Vakuum erhalt man 5,7 g der Titelverbindung: Gewerbliche Anwendbarkeit Durch die Komplexierung mit Cyclodextrinen lassen sich die eingangs genannten Benzimidazolderivate in Verbindungen überführen, die sowohl in fester als auch in gelöster Form eine hohe Lagerstabilitat aufweisen. Die erfindungsgemäßen Inklusionskomplexe stellen somit lagerfähige Verbindungen dar, die für den Einsatz in Arzneimitteln in hervorragender Weise geeignet sind. Example β-clodextrin inclusion compound with 5-methoxy-2 [(4-methoxy-3,5-dimethyl-2-pyridylmethyl) sulfinyl] - (1H) -benzimidazole 1.73 g of 5-methoxy-2 - [(4-methoxy-3,5-dimethyl-2-pyridylmethyl) sulfinyl) - (1H) -benzimidazole (5mMol) and 5.67 g of ß-cyclodextrin are mixed with 20 ml of 96% ethanol and the mixture was stirred vigorously for 15 h at an internal temperature of 30-320C. Then you cool inside from 3 h to 100C, pour over a filter and wash thoroughly with 100C cold Ethanol after. After drying in vacuo, 5.7 g of the title compound are obtained: Commercial Applicability By complexing with cyclodextrins, the initially named benzimidazole derivatives in compounds, both in solid as well as in dissolved form have a high storage stability. The invention Inclusion complexes thus represent storable connections that are necessary for use are eminently suitable in pharmaceuticals.
Von ihrer pharmakologischen Wirkung her gesehen stellen die Cyclodextrine lediglich Hilfsstoffe dar, die die therapeutischen Eigenschaften der Benzimidazolderivate (=Wirkstoffe) in keiner Weise negativ beeinflussen oder vermindern. Wie die Benzimidazolderivate selbst hemmendie erfindungsgemäßen Inklusionskomplexe deutlich die Magensauresekretion von Warmblütern und weisen darüberhinaus eine ausgezeichnete Magen- und Darmschutzwirkung bei Warmblütern auf. Diese Magen- und Darmschutzwirkung wird bereits bei der Verabreichung von Dosen beobachtet, die unterhalb der säuresekretionshemmenden Dosen liegen.From the point of view of their pharmacological effect, the cyclodextrins represent are only auxiliaries that enhance the therapeutic properties of the benzimidazole derivatives (= Active ingredients) do not negatively influence or reduce in any way. Like the benzimidazole derivatives even the inclusion complexes according to the invention markedly inhibit gastric acid secretion of warm-blooded animals and also have an excellent gastric and intestinal protective effect in warm-blooded animals. This gastric and intestinal protective effect is already used during administration observed from doses below the acid secretion inhibiting doses.
Unter Magen- und Darmschutz" wird in diesem Zusammenhang die Verhütung und Behandlung gastrointestinaler Krankheiten, insbesondere gastrointestinaler entzündlicher Krankheiten und Lasionen (wie z.B. Ulcus ventriculi, Ulcus duodeni, Gastritis, hyperazider oder medikamentös bedingter Reizmagen) verstanden, die beispielsweise durch Mikroorganismen, Bakterientoxine, Medikamente (z.B. bestimmte Antiphlogistika und Antirheumatika), Chemikalien (z.8. Ethanol), Magensaure oder Streßsituationen verursacht werden konnen.In this context, the term “stomach and intestinal protection” refers to contraception and treatment of gastrointestinal diseases, particularly gastrointestinal inflammatory ones Diseases and lesions (such as gastric ulcer, duodenal ulcer, gastritis, hyperacid or drug-induced irritable stomach) that are caused, for example, by microorganisms, Bacterial toxins, drugs (e.g. certain anti-inflammatory drugs and anti-inflammatory drugs), Chemicals (e.g. ethanol), stomach acid or stressful situations can be caused.
Aufgrund ihrer Eigenschaften sind die erfindungsgemäßen Inklusionskomplexe für den Einsatz in der Human: und Veterinärmedizin hervorragend geeignet, wobei sie insbesondere zur Behandlung und Prophylaxe von Krankheiten des Magens und Darms und solcher Krankheiten, die auf einer überhöhten Magensauresekretion beruhen, verwendet werden.Due to their properties, the inclusion complexes according to the invention are excellently suited for use in human and veterinary medicine, whereby they in particular for the treatment and prophylaxis of diseases of the stomach and intestines and diseases based on excessive gastric acid secretion are used will.
Ein weiterer Gegenstand der Erfindung sind daher die erfindungsgemäßen Inklusionskomplexe zur Anwendung bei der Behandlung und Prophylaxe von Krankheiten.The invention therefore also relates to those according to the invention Inclusion complexes for use in the treatment and prophylaxis of diseases.
Ebenso umfaßt die Erfindung die Verwendung der erfindungsgemäßen Inklusionskomplexe bei der Herstellung von Arzneimitteln.The invention likewise encompasses the use of the inclusion complexes according to the invention in the manufacture of pharmaceuticals.
Ein weiterer Gegenstand der Erfindung sind Arzneimittel, die ein oder mehrere erfindungsgemäße Inklusionskomplexe enthalten.Another object of the invention are medicaments that contain an or contain several inclusion complexes according to the invention.
Die Arzneimittel werden nach an sich bekannten, dem Fachmann geläufigen Verfahren hergestellt. Als Arzneimittel werden die erfindungsgemäßen Inklusionskomplexe entweder als solche, oder vorzugsweise in Kombination mit geeigneten pharmazeutischen Hilfsstoffen in Form von Tabletten, Dragees, Kapseln, Suppositorien, Emulsionen, Suspensionen oder Lösungen eingesetzt, wobei der Wirkstoffgehalt vorteilhafterweise zwischen 0,1 und 20X beträgt.The medicaments are made according to those known per se with which the person skilled in the art is familiar Process made. The inclusion complexes according to the invention are used as medicaments either as such, or preferably in combination with suitable pharmaceuticals Excipients in the form of tablets, coated tablets, capsules, suppositories, emulsions, Suspensions or solutions are used, the active ingredient content being advantageous is between 0.1 and 20X.
Welche Hilfsstoffe für die gewünschten Arzneimittelformulierungen geeignet sind, ist dem Fachmann aufgrund seines Fachwissens geläufig. Neben Lösemitteln, Gelbildnern, Suppositoriengrundlagen. Tabletten-Hilfsstoffen und anderen Trägern können beispielsweise Antioxidantien, Dispergiermittel, Emulgatoren, Entschaumer, Geschmackskorrigentien.Which auxiliaries for the desired pharmaceutical formulations are suitable, is familiar to the person skilled in the art on the basis of his specialist knowledge. In addition to solvents, Gel formers, suppository bases. Tablet excipients and other carriers can, for example, antioxidants, dispersants, emulsifiers, defoamers, Taste corrections.
Konservierungsmittel, Lösungsvermittler. Farbstoffe oder magensaftresistente Lacke verwendet werden.Preservatives, solubilizers. Dyes or enteric coated Varnishes are used.
Die erfindungsgemäßen Inklusionskomplexe können oral oder parenteral appliziert werden.The inclusion complexes according to the invention can be oral or parenteral be applied.
Da die Cyclodextrine die Benzimidazolderivate in ihrer therapeutischen Wirksamkeit nicht beeinträchtigen, ist es vorteilhaft, die erfindungsgemäßen Inklusionskomplexe in der Humanmedizin wie die Benzimidazolderivate selbst in einer Tagesdosis von insbesondere 0,1 bis 2,0 mg/kg Korpergewicht (bezogen auf den Wirkstoff), gegebenenfalls in Form mehrerer, vorzugsweise 1 bis 4 Einzelgaben zur Erzielung des gewunschten Ergebnisses zu verabreichen. Gegebenenfalls kann auch eine einmalige Applikation alle zwei Tage zur Anwendung kommen. Bei einer parenteralen Behandlung können ahnliche bzw. (insbesondere bei der intravenösen Verabreichung der Inklusionskomplexe) in der Regel niedrigere Dosierungen zur Anwendung kommen. Die Festlegung der jeweils erforderlichen optimalen Dosierung und Applikationsart der Inklusionskomplexe kann durch jeden Fachmann aufgrund seines Fachwissens leicht erfolgen.As the cyclodextrins the benzimidazole derivatives in their therapeutic Do not impair effectiveness, it is advantageous to use the inclusion complexes according to the invention in human medicine like the benzimidazole derivatives themselves in a daily dose of in particular 0.1 to 2.0 mg / kg body weight (based on the active ingredient), if appropriate in the form of several, preferably 1 to 4, individual doses to achieve the desired result To administer the result. If necessary, a one-time application can also be used apply every two days. In the case of parenteral treatment, similar can or (especially with the intravenous administration of the inclusion complexes) usually lower doses are used. Establishing each required optimal dosage and type of application of the inclusion complexes easily done by any skilled person on the basis of his or her specialist knowledge.
Sollen die erfindungsgemäßen Inklusionskomplexe zur Behandlung der oben genannten Krankheiten eingesetzt werden, so können die pharmazeutischen Zubereitungen auch einen oder mehrere pharmakologisch aktive Bestandteile anderer Arzneimittelgruppen, wie Antacida, beispielsweise Aluminiumhydroxid, Magnesiumaluminat; Tranquillizer, wie Benzodiazepine, beispielsweise Diazepam; Spasmolytika, wie z.B. Bietamiverin, Camylofin; Anticholinergica, wie z.B. Oxyphencyclimin, Phencarbamid; Lokalanaesthetika, wie z.B. Tetracain, Procain; gegebenenfalls auch Fermente, Vitamine oder Aminosauren enthalten.Should the inclusion complexes according to the invention for the treatment of the Above-mentioned diseases are used, so can the pharmaceutical preparations also one or more pharmacologically active components of other drug groups, such as antacids, for example aluminum hydroxide, magnesium aluminate; Tranquillizer, such as benzodiazepines, for example diazepam; Antispasmodics, such as bidamiverine, Camylofin; Anticholinergics such as oxyphencyclimine, phencarbamide; Local anesthetics, such as tetracaine, procaine; possibly also ferments, vitamins or amino acids contain.
Claims (7)
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19843427787 DE3427787A1 (en) | 1984-07-27 | 1984-07-27 | ACTIVE SUBSTANCE COMPLEXES OF 5-METHOXY-2 ((4-METHOXY-3,5-DIMETHYL-2-PYRIDYL) METHYLSULFINYL) -1H-BENZIMIDAZOLE WITH CYCLODEXTRINES, THEIR PRODUCTION AND MEDICINAL PRODUCTS |
| AU46368/85A AU4636885A (en) | 1984-07-27 | 1985-07-24 | Neue wirkstoffkomplexe |
| EP85903831A EP0190239A1 (en) | 1984-07-27 | 1985-07-24 | New active substance complexes |
| PCT/EP1985/000371 WO1986000913A1 (en) | 1984-07-27 | 1985-07-24 | New active substance complexes |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19843427787 DE3427787A1 (en) | 1984-07-27 | 1984-07-27 | ACTIVE SUBSTANCE COMPLEXES OF 5-METHOXY-2 ((4-METHOXY-3,5-DIMETHYL-2-PYRIDYL) METHYLSULFINYL) -1H-BENZIMIDAZOLE WITH CYCLODEXTRINES, THEIR PRODUCTION AND MEDICINAL PRODUCTS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE3427787A1 true DE3427787A1 (en) | 1986-01-30 |
Family
ID=6241764
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19843427787 Withdrawn DE3427787A1 (en) | 1984-07-27 | 1984-07-27 | ACTIVE SUBSTANCE COMPLEXES OF 5-METHOXY-2 ((4-METHOXY-3,5-DIMETHYL-2-PYRIDYL) METHYLSULFINYL) -1H-BENZIMIDAZOLE WITH CYCLODEXTRINES, THEIR PRODUCTION AND MEDICINAL PRODUCTS |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0190239A1 (en) |
| AU (1) | AU4636885A (en) |
| DE (1) | DE3427787A1 (en) |
| WO (1) | WO1986000913A1 (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0237200A2 (en) * | 1986-02-13 | 1987-09-16 | Takeda Chemical Industries, Ltd. | Use of basic inorganic salts of magnesium or calcium for the stabilisation of benzimidazole derivatives |
| DE3809808A1 (en) * | 1988-03-23 | 1989-10-05 | Hexal Pharma Gmbh & Co Kg | SOLIDS, ESPECIALLY FESTORAL AND RECTAL, ETOFENAMATE-CONTAINING MEDICINAL PRODUCTS |
| US5433959A (en) * | 1986-02-13 | 1995-07-18 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition |
| WO1998040069A2 (en) * | 1997-03-13 | 1998-09-17 | Hexal Ag | Stabilization of acid sensitive benzimidazoles with amino acid/cyclodextrin combinations |
| WO2003093325A1 (en) * | 2002-04-29 | 2003-11-13 | Ciba Specialty Chemicals Holding Inc. | Aqueous liquid compositions of reactive cyclodextrin derivatives and a finishing process using the said composition |
| US6749864B2 (en) | 1986-02-13 | 2004-06-15 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2026761A6 (en) * | 1990-10-31 | 1992-05-01 | Genesis Para La Investigacion | A process for the preparation of omeprazol. |
| TW224049B (en) * | 1991-12-31 | 1994-05-21 | Sunkyong Ind Ltd | |
| WO1996038175A1 (en) * | 1995-06-02 | 1996-12-05 | Takeda Chemical Industries, Ltd. | Stabilized composition comprising an antiulcerative benzimidazole |
| CN1087739C (en) * | 1998-12-28 | 2002-07-17 | 中国科学院成都有机化学研究所 | Inclusion and resolution preparation process of optical purity benzimidazoles medicines resisting peptic ulcer |
| GB2376231A (en) * | 2001-06-06 | 2002-12-11 | Cipla Ltd | Benzimidazole-cyclodextrin inclusion complex |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU176215B (en) * | 1978-01-27 | 1981-01-28 | Chinoin Gyogyszer Es Vegyeszet | Process for preparing a cyclodextrin-indomethacin inclusion complex with a ratio of at about 2:1 |
-
1984
- 1984-07-27 DE DE19843427787 patent/DE3427787A1/en not_active Withdrawn
-
1985
- 1985-07-24 WO PCT/EP1985/000371 patent/WO1986000913A1/en unknown
- 1985-07-24 EP EP85903831A patent/EP0190239A1/en not_active Withdrawn
- 1985-07-24 AU AU46368/85A patent/AU4636885A/en not_active Abandoned
Cited By (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5639478A (en) * | 1986-02-13 | 1997-06-17 | Takeda Chemical Industries, Ltd. | Method to stabilize a pharmaceutical composition and its production |
| EP0446961A3 (en) * | 1986-02-13 | 1992-04-01 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition and its production |
| US6380234B1 (en) | 1986-02-13 | 2002-04-30 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition and its production |
| EP0423748A1 (en) * | 1986-02-13 | 1991-04-24 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition and its production |
| US6296875B1 (en) | 1986-02-13 | 2001-10-02 | Takeda Chemical Industries, Ltd. | Method for producing a granule |
| EP0446961A2 (en) * | 1986-02-13 | 1991-09-18 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition and its production |
| EP0237200A3 (en) * | 1986-02-13 | 1988-02-03 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition comprising a benzimidazole compound, its production and its use as an antiulcer agent |
| US5433959A (en) * | 1986-02-13 | 1995-07-18 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition |
| US5045321A (en) * | 1986-02-13 | 1991-09-03 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition and its production |
| US6749864B2 (en) | 1986-02-13 | 2004-06-15 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition |
| EP0237200A2 (en) * | 1986-02-13 | 1987-09-16 | Takeda Chemical Industries, Ltd. | Use of basic inorganic salts of magnesium or calcium for the stabilisation of benzimidazole derivatives |
| US5879708A (en) * | 1986-02-13 | 1999-03-09 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition |
| US6017560A (en) * | 1986-02-13 | 2000-01-25 | Takeda Chemical Industries, Ltd. | Process for producing stabilized pharmaceutical composition |
| US6123962A (en) * | 1986-02-13 | 2000-09-26 | Takeda Chemical Industries, Inc. | Process for producing stabilized pharmaceutical composition |
| US6521256B2 (en) | 1986-02-13 | 2003-02-18 | Takeda Chemical Industries, Ltd. | Stabilized pharmaceutical composition |
| DE3809808A1 (en) * | 1988-03-23 | 1989-10-05 | Hexal Pharma Gmbh & Co Kg | SOLIDS, ESPECIALLY FESTORAL AND RECTAL, ETOFENAMATE-CONTAINING MEDICINAL PRODUCTS |
| WO1998040069A3 (en) * | 1997-03-13 | 1998-12-17 | Hexal Ag | Stabilization of acid sensitive benzimidazoles with amino acid/cyclodextrin combinations |
| US6248758B1 (en) * | 1997-03-13 | 2001-06-19 | Hexal Ag | Pharmaceutical antacid |
| AU731186B2 (en) * | 1997-03-13 | 2001-03-29 | Hexal Ag | Stabilization of acid sensitive benzimidazols with amino acid/cyclodextrin combinations |
| CN1113649C (en) * | 1997-03-13 | 2003-07-09 | 赫克萨尔股份公司 | Stabilization of acid sensitive benzimidazoles with amino acid/cyclodextrin combinations |
| WO1998040069A2 (en) * | 1997-03-13 | 1998-09-17 | Hexal Ag | Stabilization of acid sensitive benzimidazoles with amino acid/cyclodextrin combinations |
| WO2003093325A1 (en) * | 2002-04-29 | 2003-11-13 | Ciba Specialty Chemicals Holding Inc. | Aqueous liquid compositions of reactive cyclodextrin derivatives and a finishing process using the said composition |
| CN100335507C (en) * | 2002-04-29 | 2007-09-05 | 西巴特殊化学品控股有限公司 | Aqueous liquid compositions of reactive cyclodextrin derivatives and a finishing process using the said composition |
Also Published As
| Publication number | Publication date |
|---|---|
| AU4636885A (en) | 1986-02-25 |
| EP0190239A1 (en) | 1986-08-13 |
| WO1986000913A1 (en) | 1986-02-13 |
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