WO1991001735A1 - Combined preparation consisting of gallopamil and xipamide - Google Patents

Combined preparation consisting of gallopamil and xipamide Download PDF

Info

Publication number
WO1991001735A1
WO1991001735A1 PCT/EP1990/001191 EP9001191W WO9101735A1 WO 1991001735 A1 WO1991001735 A1 WO 1991001735A1 EP 9001191 W EP9001191 W EP 9001191W WO 9101735 A1 WO9101735 A1 WO 9101735A1
Authority
WO
WIPO (PCT)
Prior art keywords
gallopamil
xipamide
combined preparation
acid
preparation consisting
Prior art date
Application number
PCT/EP1990/001191
Other languages
German (de)
French (fr)
Inventor
Heinz Einig
Ernst Raab
Norbert Pfannkuch
Original Assignee
Knoll Aktiengesellschaft
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 Knoll Aktiengesellschaft filed Critical Knoll Aktiengesellschaft
Publication of WO1991001735A1 publication Critical patent/WO1991001735A1/en

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
    • A61K31/275—Nitriles; Isonitriles

Definitions

  • the invention relates to a combination preparation of gallopamil and xipamide.
  • gallopamil [(3,4-dimethoxyphenethyl) methylamino [-2-isopropyl-2- (3,4,5-trimethoxyphenyl) valeronitrile, DE 1 154 810) et al. suitable for the prophylaxis and long-term therapy of chronic coronary sufficiency and angina pectoris (cf. Rote Liste 1988 No. 26 094).
  • xipamide (4-chloro-2 ', 6'-dimethyl-5-sulfamoyl-salicylamide, DE 1 270 544) has good diuretic properties and is used against hypertension (Red List 1988 No. 35 037).
  • the invention relates to a medicament which contains gallopamil and xipamide in a weight ratio of 25: 1 to 3: 1.
  • the weight ratio of gallopamil to xipamide is preferably between 20: 1 and 5: 1.
  • the gallopamil is preferably used as the salt for the combination.
  • hydrobromic acid, phosphoric acid, sulfuric acid, oxalic acid, maleic acid, fu aric acid, lactic acid, tartaric acid, adipic acid, benzene acid and especially hydrochloric acid are suitable for salt formation.
  • the gallopamil or its salt is preferably used as a depot form in the combination.
  • the medicinal product contains the two active substances together and is used in the form of tablets, film-coated tablets, capsules or coated tablets. These shapes can be produced in the usual way.
  • the new combination has a surprisingly good hypotensive effect. It can therefore be used well for the treatment of high blood pressure. This is particularly true in the area of renal failure patients. example 1
  • Tablets of the following composition were pressed in a conventional manner on a tablet press:
  • the active ingredients would be mixed together with corn starch and milk sugar, then granulated with an alcoholic solution of hydroxymethylpropyl cellulose. After admixing magnesium stearate and cellulose, tablets weighing 200 mg were pressed in a conventional manner. The tables were then coated with a film varnish made of hydroxymethylpropyl cellulose, which contained polyethylene glycol 400 as an additive and talc and titanium dioxide as a pigment.
  • Gallopami® HC1, Na alginate and ®Eudragit RL were mixed dry in a mixer, moistened with an aqueous solution of PVP while stirring, passed through a sieve and in one
  • Fluidized bed dryer dried, passed through a sieve again and mixed with Mg stearate and cellulose powder.
  • ®Eudragit RL is a polyacrylic ethacrylic acid ester from Röh Pharma GmbH, Darmstadt. b) Analogously to a), granules of the following composition were produced:
  • the first four ingredients were mixed, granulated with an ethanolic solution of PVP, dried, sieved and then mixed with magnesium stearate.
  • Bolus tablets of the composition of Example 2a were prepared in a conventional manner and filled into hard gelatin capsules on a capsule filling machine together with a mixture of 45 mg lactose and 5 mg xipamide.
  • the bolus tablets had an oblong format with the dimensions 6 mm x 15 m.

Landscapes

  • Health & Medical Sciences (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)

Abstract

Combined preparation consisting of gallopamil and xipamide and its use as a drug.

Description

Kombinationspräparat aus Gallopamil und XipamidCombination preparation of gallopamil and xipamide
Beschreibungdescription
Die Erfindung betrifft ein Kombinationspräparat aus Gallopamil und Xipamid.The invention relates to a combination preparation of gallopamil and xipamide.
Es ist bekannt, daß sich Gallopamil (5-[(3,4-Dimethoxyphenethyl)methyl- amino[-2-isopropyl-2-(3,4,5-trimethoxyphenyl)valeronitril, DE 1 154 810) u.a. zur Prophylaxe und Langzeittherapie von chronischer Koronarin¬ suffizienz und Angina pectoris eignet (vgl. Rote Liste 1988 Nr. 26 094). Weiter ist bekannt, daß Xipamid (4-Chlor-2',6'-dimethyl-5-sulfamoyl- salicylamid, DE 1 270 544) gute diuretische Eigenschaften besitzt und gegen Hypertonie eingesetzt wird (Rote Liste 1988 Nr. 35 037).It is known that gallopamil (5 - [(3,4-dimethoxyphenethyl) methylamino [-2-isopropyl-2- (3,4,5-trimethoxyphenyl) valeronitrile, DE 1 154 810) et al. suitable for the prophylaxis and long-term therapy of chronic coronary sufficiency and angina pectoris (cf. Rote Liste 1988 No. 26 094). It is also known that xipamide (4-chloro-2 ', 6'-dimethyl-5-sulfamoyl-salicylamide, DE 1 270 544) has good diuretic properties and is used against hypertension (Red List 1988 No. 35 037).
Es wurde nun gefunden, daß beide Wirkstoffe in Kombination miteinander überraschende Wirkungen zeigen.It has now been found that the two active compounds, in combination with one another, have surprising effects.
Gegenstand der Erfindung ist ein Arzneimittel, welches Gallopamil und Xipamid in Gewichtsverhältnis von 25 : 1 bis 3 : 1 enthält.The invention relates to a medicament which contains gallopamil and xipamide in a weight ratio of 25: 1 to 3: 1.
Das Gewichtsverhältnis von Gallopamil zu Xipamid liegt vorzugsweise zwischen 20 : 1 und 5 : 1.The weight ratio of gallopamil to xipamide is preferably between 20: 1 and 5: 1.
Das Gallopamil wird vorzugsweise als Salz für die Kombination verwendet. Zur Salzbildung kommen beispielsweise Bromwasserstoffsäure, Phosphorsäure, Schwefelsäure, Oxalsäure, Maleinsäure, Fu arsäure, Milchsäure, Weinsäure, Adipinsäure, Benzolsäure und insbesondere Salzsäure in Betracht.The gallopamil is preferably used as the salt for the combination. For example, hydrobromic acid, phosphoric acid, sulfuric acid, oxalic acid, maleic acid, fu aric acid, lactic acid, tartaric acid, adipic acid, benzene acid and especially hydrochloric acid are suitable for salt formation.
Das Gallopamil bzw. dessen Salz wird vorzugsweise als Depotform in die Kombination eingesetzt.The gallopamil or its salt is preferably used as a depot form in the combination.
Das Arzneimittel enthält die beiden Wirkstoffe zusammen und wird in Form von Tabletten, Fi mtabletten, Kapseln oder Dragees angewendet. Diese Formen lassen sich in üblicher Weise herstellen.The medicinal product contains the two active substances together and is used in the form of tablets, film-coated tablets, capsules or coated tablets. These shapes can be produced in the usual way.
Die neue Kombination besitzt eine überraschend gute blutdrucksenkende Wirkung. Sie läßt sich daher gut zur Behandlung des Blutdruckhochdrucks verwenden. Das gilt besonders im Bereich niereninsuffizienter Patienten. Beispiel 1The new combination has a surprisingly good hypotensive effect. It can therefore be used well for the treatment of high blood pressure. This is particularly true in the area of renal failure patients. example 1
Auf einer Tablettenpresse wurden in üblicher Weise Tabletten folgender Zusammensetzung gepreßt:Tablets of the following composition were pressed in a conventional manner on a tablet press:
50 mg Gallopamil-Hydrochlorid 5 mg Xipamid 100 mg Maisstärke 30 mg Milchzucker 5 mg Hydroxy ethylpropylcellulose 1 mg Magnesiumstearat 9 mg Cellulose50 mg gallopamil hydrochloride 5 mg xipamide 100 mg corn starch 30 mg lactose 5 mg hydroxyethyl propyl cellulose 1 mg magnesium stearate 9 mg cellulose
Die Wirkstoffe würden zusammen mit Maisstärke und Milchzucker gemischt, dann mit einer alkoholischen Lösung von Hydroxymethylpropylcellulose granuliert. Nach Zumischung von Magnesiumstearat und Cellulose wurden in herkömmlicher Art Tabletten mit einem Gewicht von 200 mg gepreßt. Die Tabellen wurden anschließend mit einem Filmlack aus Hydroxymethylpropyl¬ cellulose, der als Zusatzstoff Polyethylenglykol 400 und als Pigment Talkum und Titandioxid enthielt, überzogen.The active ingredients would be mixed together with corn starch and milk sugar, then granulated with an alcoholic solution of hydroxymethylpropyl cellulose. After admixing magnesium stearate and cellulose, tablets weighing 200 mg were pressed in a conventional manner. The tables were then coated with a film varnish made of hydroxymethylpropyl cellulose, which contained polyethylene glycol 400 as an additive and talc and titanium dioxide as a pigment.
Beispiel 2Example 2
a) Es wurden in üblicher Weise ein Granulat folgender Zusammensetzung (in mg) hergestellt:a) Granules of the following composition (in mg) were produced in the usual way:
Gallopamil-HC1 100Gallopamil-HC1 100
Na-Alginat 240Na alginate 240
©Eudragit RL 92 PVP 13© Eudragit RL 92 PVP 13
Mg-Stearat 4Mg stearate 4
Cellulosepulver 31Cellulose powder 31
Dazu wurden Gallopami «HC1, Na-Alginat und ®Eudragit RL trocken in einem Mischer gemischt, unter Rühren mit einer wäßrigen Lösung von PVP befeuchtet, durch ein Sieb getrieben und in einemFor this purpose, Gallopami® HC1, Na alginate and ®Eudragit RL were mixed dry in a mixer, moistened with an aqueous solution of PVP while stirring, passed through a sieve and in one
Wirbelschichttrockner getrocknet, erneut über ein Sieb gegeben und mit Mg-Stearat und Cellulosepulver vermischt.Fluidized bed dryer dried, passed through a sieve again and mixed with Mg stearate and cellulose powder.
®Eudragit RL ist ein Polyacryl ethacrylsäureester der Firma Röh Pharma GmbH, Darmstadt. b) Analog a) wurde ein Granulat folgender Zusammensetzung hergestel lt :®Eudragit RL is a polyacrylic ethacrylic acid ester from Röh Pharma GmbH, Darmstadt. b) Analogously to a), granules of the following composition were produced:
Figure imgf000005_0001
Die vier zuerst genannten Bestandteile wurden gemischt, mit einer ethanolischen Lösung von PVP granuliert, getrocknet, gesiebt und anschließend mit Magnesiumstearat vermischt.
Figure imgf000005_0001
The first four ingredients were mixed, granulated with an ethanolic solution of PVP, dried, sieved and then mixed with magnesium stearate.
c) In einer Zweischichttablettenpresse wurden Tabletten gepreßt, deren erste Schicht 480 mg Gallopamil-Granulat und deren zweite Schicht 100 mg Xipamid-Granulat enthielt. Die so erhaltenen Tabletten mit 100 mg Gallopamil und 10 mg Xipamid wurden anschließend analog Beispiel 1 mit einem Lack überzogen.c) Tablets were pressed in a two-layer tablet press, the first layer of which contained 480 mg of gallopamil granules and the second layer of which contained 100 mg of xipamide granules. The tablets obtained in this way with 100 mg gallopamil and 10 mg xipamide were then coated with a lacquer analogously to Example 1.
Beispiel 3Example 3
Es wurden in üblicher Weise Bolus-Tabletten der Zusammensetzung des Beispiels 2a hergestellt und auf einer Kapselabfüllmaschine zusammen mit einer Mischung aus 45 mg Lactose und 5 mg Xipamid in Hartgelatinesteckkapseln abgefüllt. Die Bolus-Tabletten hatten ein Oblong-Format mit den Abmessungen 6 mm x 15 m. Bolus tablets of the composition of Example 2a were prepared in a conventional manner and filled into hard gelatin capsules on a capsule filling machine together with a mixture of 45 mg lactose and 5 mg xipamide. The bolus tablets had an oblong format with the dimensions 6 mm x 15 m.

Claims

Patentansprüche Claims
1. Arzneimittel, enthaltend Gallopamil und Xipamid im Gewichtsverhältnis von 25 : 1 bis 3 : 1.1. Medicament containing gallopamil and xipamide in a weight ratio of 25: 1 to 3: 1.
2. Verfahren zur Herstellung eines Arzneimittels, dadurch gekennzeichnet, daß man Gallopamil und Xipamid im Verhältnis 25 : 1 bis 3 A in eine galenische Appli ationsform einarbeitet. 2. A process for the manufacture of a medicament, characterized in that gallopamil and xipamide are incorporated in a galenic application form in a ratio of 25: 1 to 3 A.
PCT/EP1990/001191 1989-07-29 1990-07-20 Combined preparation consisting of gallopamil and xipamide WO1991001735A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DEP3925252.3 1989-07-29
DE3925252A DE3925252A1 (en) 1989-07-29 1989-07-29 COMBINATION PREPARATION OF GALLOPAMIL AND XIPAMID

Publications (1)

Publication Number Publication Date
WO1991001735A1 true WO1991001735A1 (en) 1991-02-21

Family

ID=6386182

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1990/001191 WO1991001735A1 (en) 1989-07-29 1990-07-20 Combined preparation consisting of gallopamil and xipamide

Country Status (4)

Country Link
AU (1) AU5958790A (en)
DE (1) DE3925252A1 (en)
WO (1) WO1991001735A1 (en)
ZA (1) ZA905912B (en)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0301373A2 (en) * 1987-07-25 1989-02-01 Knoll Ag Products containing gallopamil and prazosine

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0301373A2 (en) * 1987-07-25 1989-02-01 Knoll Ag Products containing gallopamil and prazosine

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Unlisted Drugs, Band 23, Nr. 12, Dezember 1971, Chatham, New Jersey (US) siehe seite 178d *

Also Published As

Publication number Publication date
ZA905912B (en) 1992-03-25
AU5958790A (en) 1991-03-11
DE3925252A1 (en) 1991-01-31

Similar Documents

Publication Publication Date Title
DE3132614C2 (en) Suspension of microencapsulated bacampicillin acid addition salt for oral, especially pediatric, administration and powder for their preparation
DE3030622C2 (en) Divisible prolonged-release tablet for the delivery of metoprolol or oxprenolol
DE69727000T2 (en) Delayed-release medicines containing venlafaxine
AT396329B (en) PHARMACEUTICAL GRANULES AND METHOD FOR THE PRODUCTION THEREOF
DE19541128C2 (en) Stabilized thyroid hormone-containing medicines
DE60025536T2 (en) COATING OF TABLET CORE
DE19648576C2 (en) Lozenge for modified release of active substances in the gastrointestinal tract
DE3152519T1 (en) NEW FENOFIBRATE FINISHED PREPARATION, ITS PRODUCTION PROCESS, ITS APPLICATION AS A MEDICINE
DE2323686A1 (en) LONG-TERM EFFECTIVE MEDICINAL PREPARATION FORM AND METHOD FOR MANUFACTURING IT
CH655241A5 (en) METHOD FOR PRODUCING THERAPEUTICALLY EFFECTIVE PREPARATIONS WITH CONTINUOUS PROCESS OF THE ACTIVE SUBSTANCE RELEASE.
DE2414868A1 (en) MEDICINAL PRODUCTS AND METHOD FOR ITS MANUFACTURING
DD292837A5 (en) PROCESS FOR PREPARING CHOLESTYRAMINE TABLETS
DE69814850T2 (en) PARACETAMOL CONTAINING SLICKABLE TABLET
DE3435325A1 (en) LONG-TERM THEOPHYLLIN TABLET AND METHOD FOR THE PRODUCTION THEREOF
DE69530759T2 (en) FILM COATED TABLET CONTAINING PARACETAMOL AND DOMPERIDONE
WO1991003249A1 (en) Preparations containing colestyramine for reducing lipid levels
EP1928459A2 (en) Tablet-type controlled-release preparation containing cinnarizine and dimenhydrinate for combating vertigo
CH669523A5 (en)
WO2003101430A1 (en) Pharmaceutical composition containing oxcarbazepine and having a controlled active substance release
EP0722719B1 (en) Process for preparing flavano-lignan preparations
EP0471967A1 (en) Chewable tablet containing sucralfate
EP1135147B1 (en) Method for producing medicaments from plant extracts, in a solid form of administration
WO1991001735A1 (en) Combined preparation consisting of gallopamil and xipamide
EP0219728B1 (en) Preparation on the basis of a mixture
CH648209A5 (en) COMBINATION OF MEDICINAL PRODUCTS FOR TREATING INFECTIOUS RESPIRATORY DISEASES.

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU CA FI HU JP KR NO US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB IT LU NL SE

NENP Non-entry into the national phase

Ref country code: CA