DE4041559A1 - Novel anti-cholinergic agents contg. quat. ammonium gps. - used to limit side effects of administration of opiate(s) and opioid(s) - Google Patents

Novel anti-cholinergic agents contg. quat. ammonium gps. - used to limit side effects of administration of opiate(s) and opioid(s)

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Publication number
DE4041559A1
DE4041559A1 DE19904041559 DE4041559A DE4041559A1 DE 4041559 A1 DE4041559 A1 DE 4041559A1 DE 19904041559 DE19904041559 DE 19904041559 DE 4041559 A DE4041559 A DE 4041559A DE 4041559 A1 DE4041559 A1 DE 4041559A1
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Germany
Prior art keywords
side effects
opiate
opiates
anticholinergic
opioids
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.)
Withdrawn
Application number
DE19904041559
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German (de)
Inventor
Michael Dr Herschel
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.)
Boehringer Ingelheim GmbH
Original Assignee
Boehringer Ingelheim GmbH
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Filing date
Publication date
Application filed by Boehringer Ingelheim GmbH filed Critical Boehringer Ingelheim GmbH
Priority to DE19904041559 priority Critical patent/DE4041559A1/en
Publication of DE4041559A1 publication Critical patent/DE4041559A1/en
Withdrawn legal-status Critical Current

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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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine

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  • Health & Medical Sciences (AREA)
  • Emergency Medicine (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)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Anticholinergic agents contg. quaternary ammonium gps. are used for prodn. of medicament prepns. for limitation of side effects of opiates/opioids. Analgesic compsns. contg. the anticholinergic agents and an opiate/opiod are also new. The anticholinergic agent is esp. butyl(nor)scopolaminium bromide, N-methyl-scopolaminium bromide, trospium chloride or cimetropium, chloride opiate/opiod is morphine, biprenorphine, hydrocodone or heroin. USE/ADVANTAGE - The anticholinergic agents are used to prevent side effects on the peripheal and central nervous systems and in the gastrointestinal tract leading to colics. Dosage is esp. 15-25 (esp. 20) mg., i.m. or i.v.

Description

Die Erfindung betrifft die gemeinsame Anwendung von Opiaten/Opioiden und bestimmter Anticholinergika.The invention relates to the common application of Opiates / opioids and certain anticholinergics.

Morphin und die mit Morphin verwandten Substanzen (Opiate/Opioide) haben neben ihrer analgetischen Wirkung vielfältige Wirkungen auf das periphere (und zentrale) Nervensystem.Morphine and the substances related to morphine (Opiates / opioids) have in addition to their analgesic Effect manifold effects on the peripheral (and central) nervous system.

Bei den peripheren Nebenwirkungen sind solche an der glatten Muskulatur des Gastrointestinaltraktes nicht selten und können sich gegebenenfalls sogar als Koliken manifestieren.The peripheral side effects are those of the smooth muscles of the gastrointestinal tract are not rare and may even develop as colic manifest.

Daher wird seit langer Zeit bei verschiedenen Opiaten gleichzeitig ein Anticholinergikum gegeben, um die unerwünschten Nebenwirkungen dieser Art auszuschalten.Therefore, various opiates have been used for a long time given an anticholinergic at the same time eliminate undesirable side effects of this type.

Traditionsgemäß ist dieses Anticholinergikum Atropin. Bekannt ist beispielsweise seit 1954 die gemeinsame Anwendung von Dilaudid und Atropin. Atropin aber hat für sich genommen starke zentralnervöse Nebenwirkungen, die entsprechend der Dosis zu schweren Zwischenfällen führen können.This anticholinergic is traditionally atropine. For example, the common one has been known since 1954 Use of dilaudide and atropine. But has atropine individually strong central nervous side effects, which, according to the dose, lead to serious incidents being able to lead.

Es wurde nun gefunden, daß überraschenderweise Anticholinergika, die eine quartäre Ammoniumgruppe enthalten, für die gemeinsame Anwendung mit Opiaten/Opioiden besonders gut geeignet sind.It has now been found that, surprisingly Anticholinergics, which are a quaternary ammonium group included for common use with Opiates / opioids are particularly suitable.

Wie sich gezeigt hat, können solche Anticholinergika nicht nur separat gleichzeitig (bzw. in engem zeitlichem Zusammenhang) mit Opiaten/Opioiden angewendet werden, sondern auch in fixen Kombinationen.As has been shown, such anticholinergics  not only separately at the same time (or in close temporal relationship) with opiates / opioids be used, but also in fixed combinations.

Als Opiate/Opioide können im Sinne der Erfindung z. B. verwendet werden:As opiates / opioids for the purposes of the invention, for. B. be used:

Morphin
Buprenorphin
Hydromorphon
Hydrocodon
Heroin.Morphine
Buprenorphine
Hydromorphone
Hydrocodone
Heroin.

Geeignete Anticholinergika sind beispielsweise:Suitable anticholinergics include:

N-Butylscopolaminiumbromid
N-Methyscopolaminiumbromid
Trospiumchlorid
Cimetropiumchlorid.N-butylscopolaminium bromide
N-methyscopolaminium bromide
Trospium chloride
Cimetropium chloride.

Die Opiate/Opioide wie auch die Anticholinergika werden in der üblichen Dosierung angewendet. Abweichungen nach oben und unten sind jedoch möglich. Insbesondere N-Butylscopolaminiumbromid (Handelsname BUSCOPAN®) kann in Mengen verabreicht werden, die deutlich oberhalb der therapeutischen Dosen liegen. Im allgemeinen beträgt die erfindungsgemäße Einzeldosis dieser Verbindung bei parenteraler Anwendung 15-25, vorzugsweise 20 mg i.m. oder i.v..The opiates / opioids as well as the anticholinergics applied in the usual dosage. Deviations after however, top and bottom are possible. In particular N-butylscopolaminium bromide (trade name BUSCOPAN®) can be administered in amounts that are significant are above the therapeutic doses. in the in general, the single dose according to the invention is this connection in parenteral use 15-25, preferably 20 mg i.m. or i.v ..

Die erfindungsgemäß verwendbaren Anticholinergika wie auch die erfindungsgemäßen Kombinationen werden mit gebräuchlichen Hilfs- und/oder Trägerstoffen zu üblichen Zubereitungen verarbeitet.The anticholinergics that can be used according to the invention, such as the combinations according to the invention are also included common auxiliaries and / or carriers usual preparations processed.

Beispiele:Examples: 1. Injektionslösung1. Solution for injection

Eine isotonische Kochsalzlösung mit einem Gehalt von 2 mg Hydromorphon und 10 mg Butylscopolaminiumbromid pro ml wird nach Zusatz von 0,2 mg pro ml p-Hydroxybenzoesäuremethylester filtriert und zu je 2 ml unter aseptischen Bedingungen in Ampullen gefüllt. Die Ampullen werden sterilisiert und verschlossen.An isotonic saline solution with a content of 2 mg hydromorphone and 10 mg Butylscopolaminium bromide per ml is added after of 0.2 mg per ml of methyl p-hydroxybenzoate filtered and 2 ml each under aseptic Conditions filled in ampoules. The ampoules are sterilized and sealed.

2. Injektionslösung2. Solution for injection

 0,5 Gew.-Teile Morphin
20,0 Gew.-Teile Butylscopolaminiumbromid
 1,0 Gew.-Teile Dinatriumsalz der Ethylendiamintetraessigsäure
 8,5 Gew.-Teile Natriumchlorid
doppelt destilliertes Wasser ad 1000 Gew.-Teile.0.5 part by weight of morphine
20.0 parts by weight of butylscopolaminium bromide
1.0 part by weight of disodium salt of ethylenediaminetetraacetic acid
8.5 parts by weight of sodium chloride
double distilled water ad 1000 parts by weight.

Die aus den Bestandteilen in üblicher Weise hergestellte Lösung wird in Mengen von 1 ml entsprechend dem vorstehenden Beispiel in Ampullen verpackt.The from the ingredients in the usual way prepared solution is in amounts of 1 ml according to the above example in ampoules packed up.

3. Tabletten3. tablets

 1,0 Gew.-Teile Buprenorphin
20,0 Gew.-Teile Butylscopolaminiumbromid
30,0 Gew.-Teile Milchzucker
43,0 Gew.-Teile Maisstärke
 5,0 Gew.-Teile lösliche Stärke
 1,0 Gew.-Teile Magnesiumstearat1.0 part by weight of buprenorphine
20.0 parts by weight of butylscopolaminium bromide
30.0 parts by weight of milk sugar
43.0 parts by weight of corn starch
5.0 parts by weight of soluble starch
1.0 part by weight of magnesium stearate

Wirkstoffe und Magnesiumstearat werden mit einer wäßrigen Lösung der löslichen Stärke granuliert, das Granulat wird getrocknet und gründlich mit dem Milchzucker und der Maisstärke vermischt.Active ingredients and magnesium stearate are combined with a granulated aqueous solution of the soluble starch, the granules are dried and thoroughly cleaned with the Milk sugar and cornstarch mixed.

Das Gemisch wird dann zu Tabletten von 100 mg Gewicht verpreßt, so daß jede Tablette 1 mg Buprenorphin und 20 mg Butylscopolaminiumbromid enthält.The mixture then becomes 100 mg tablets Weight pressed so that each tablet 1 mg Buprenorphine and 20 mg butylscopolaminium bromide contains.

Claims (6)

1. Verwendung von Anticholinergika, die eine quartäre Ammoniumgruppe enthalten, bei der Herstellung von Arzneimittelzubereitungen zur Verminderung der Nebenwirkung von Opiaten/Opioiden.1. Use of anticholinergics that are a quaternary Contain ammonium group in the manufacture of Medicinal preparations for reducing the Side effect of opiates / opioids. 2. Verwendung von Wirkstoffkombinationen aus Opiaten/Opioiden und Anticholinergika mit einer quartären Ammoniumgruppe bei der Herstellung von Arzneimittelzubereitungen mit analgetischer Wirkung und verminderten Nebenwirkungen auf das periphere und zentrale Nervensystem.2. Use of active ingredient combinations Opiates / opioids and anticholinergics with one quaternary ammonium group in the manufacture of Medicinal preparations with analgesic Effect and reduced side effects on it peripheral and central nervous system. 3. Verwendung nach Anspruch 1 oder 2, dadurch gekennzeichnet, daß das Anticholinergikum Butylnorscopolaminiumbromid ist.3. Use according to claim 1 or 2, characterized characterized that the anticholinergic Butylnorscopolaminium bromide. 4. Analgetische Mittel, gekennzeichnet durch einen Gehalt an einem Opiat/Opioid und einem Anticholinergikum, das eine quartäre Ammoniumgruppe enthält.4. Analgesic agent, characterized by a Content of one opiate / opioid and one Anticholinergic, which is a quaternary Contains ammonium group. 5. Mittel nach Anspruch 4, dadurch gekennzeichnet, daß das Anticholinergikum Butylscopolaminium­ bromid, N-Methylscopolaminiumbromid, Trospiumchlorid oder Cimetropiumchlorid ist.5. Composition according to claim 4, characterized in that the anticholinergic butylscopolaminium bromide, N-methylscopolaminium bromide, Is trospium chloride or cimetropium chloride. 6. Mittel nach Anspruch 5, dadurch gekennzeichnet, daß die Opiate/Opioide Morphin, Buprenorphin, Hydrocodon oder Heroin sind.6. Composition according to claim 5, characterized in that the opiates / opioids morphine, buprenorphine, Are hydrocodone or heroin.
DE19904041559 1990-12-22 1990-12-22 Novel anti-cholinergic agents contg. quat. ammonium gps. - used to limit side effects of administration of opiate(s) and opioid(s) Withdrawn DE4041559A1 (en)

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DE4041559A1 true DE4041559A1 (en) 1992-06-25

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8946290B2 (en) 2001-09-18 2015-02-03 Gruenenthal Gmbh Combination of selected opioids with muscarine antagonists for treating urinary incontinence

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8946290B2 (en) 2001-09-18 2015-02-03 Gruenenthal Gmbh Combination of selected opioids with muscarine antagonists for treating urinary incontinence

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