CA1042796A

CA1042796A - Therapeutic composition containing a psychosedative and an antacid

Info

Publication number: CA1042796A
Application number: CA226,816A
Authority: CA
Inventors: Wolfgang Bilhuber; Paul Rados
Original assignee: F Hoffmann La Roche AG
Current assignee: F Hoffmann La Roche AG
Priority date: 1974-05-16
Filing date: 1975-05-13
Publication date: 1978-11-21
Also published as: FR2270886A1; AR212907A1; PH13370A; FR2270886B1; NL7504704A; DE2517585A1

Abstract

ABSTRACT

A process for the manufacture of a medicament, which process comprises mixing together a psychosedative from the benzodiazepine series, an antacid and an antiflatulent and, if desired, a carrier material and/or adjuvant suitable for therapeutic administration.

Description

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The present invention is concerned with medicaments and a process for the manufacture thereof.
The medicaments provided by the present invention contain as the active ingredients a psychosedative from the benzodiazepine series, from 50 to 1000 parts by weight of an antacid and from 10 to 150 parts by weight of an antiflatulent per part by weight of psychosedative and, optionally, a compatible carrier material or adjuvant or both suitable for therapeutic administration.
Of the customary antacids which can be present in the medicaments provided by the present invention, there may be mentioned, in particular, salts, hydroxides and oxides of metals of the first to third group of the periodic system as well as mixtures and coprecipitates thereof. Preferred antacids for the purpose of the present invention are aluminium hydroxide (especially colloidal), aluminium glycinate, aluminium silicate, calcium silicate, calcium carbonate, magnesium oxide, magnesium hydroxide, magnesium carbonate, magnesium silicate, sodium bicarbonate and potassium carbonateO
Especially preferred are aluminium hydroxide/magnesium carbonate coprecipitate - and magnesium oxide as well as, in particular, mixtures thereof, with a quantitative ratio of 5:1 being especially favourableO
2a Of the customary antiflatulents which can be present in the `;~ medicaments provided by the present invention, there may be mentioned, in particular, polysiloxanesO Especially ~ ' 1~34;~79~6 preferred is dimethylpolysiloxane, which is used, in particular, in the form of Medic.~l ~ntifoam (~imethicone).

Psychosedatives from the benzodiazepine series suitable for use in the present invention are, inter alia, 7-chloro-

-2-methylamino~5-phenyl-3H-1,4-benzodiazepine 4-oxide (chlordiazepoxide), 7-chloro-1,3-dihydro-1-methyl-5-phenyl--2H-1,4-benzodiazepin-~-one (diazepam), 7-chloro-2,3-dihydro--l-methyl-5-phenyl-lH-1,4-benzodiazepine (medazepam), 7-bromo--1,3-dihydro-5-(2-pyridyl)-2H-1,4-benzodiazepin-2-one (bromazepam) 10-chloro-llb-(2-chlorophenyl)-2,3,5,1lb--tetrahydrooxazolo[3,2-d][1,4]benzodiazepin-6(7H)-one (cloxazolazepam), 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-

-3-hydroxy-2H-1,4-benzodiazepin-2-one (lorazepam), 7-chloro--1,3-dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one (oxazepam), 10-chloro-2,3,5,11b-tetrahydro-2-methyl-llb--phenyloxazolo [3,2-d][1,4]benzodiazepin-6(7H)-one (oxazolazepam), 7-chloro-1-cyclopropylmethyl-1,3-dihydro-5-phenyl-2H-1,4--benzodiazepin-2-one (prazepam) and 7-chloro-1,3-dihydro-3--hydroxy-l-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one (temazepam~ as well as analogues thereof. The said psychosedatives can also be present in the form of pharmaceutically acceptable salts.

The quantitative ratio of the active ingredients in the medicaments provided by the present invention can vary within ~9S' /~ C-:~eC( abDve, relatively wide limits.~ From about 50 to 1000 parts by weight of antacid and from 10 to 150 parts by weight of antiflatulent are oxpr~i ntll presert per part by weight of psychosedetive.

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~34'~796 Preferably from lO0 to 700 parts by weight of antacid and from 15 to 125 parts by weight of antiflatulent are present per part by weight of p~ychosedative.

A preferred unit dosage for adults contains from 0.5 to 5 mg of psychosedative,from 500 to 700 mg of antacid and from 75 to 125 mg of antiflatulent.

~he medicaments provided by the present invention are intended for the treatment of gastric hyperacidity and its effects (heartburn, peptic ulcer) as well as of a feeling of repletion and flatulence resulting from aerophagia and meteorism.

~hese symptoms are very frequently an expression or concomitant symptom of an emotional disturbance. ~hus, a significant relation between emotional stress and increased production of hydrochloric acid and pepsin has been demonstrated by numerous researchers. Moreover, not only practical clinical experience but also objective studies substantiate the important role played by the "nervous element" in aerophagia.

From the causative role of psychic factors in the pathogenesis of the said disturbances, it is evident that their effective treatment should not be limited to the symptomatic influence on the local occurrence by the administration of antacids and antiflatulents but, rather, that suitable measures should also be taken for the elimination of the basic psychic disturbance.

~)4~:796 It is known, however, that the basic salts used as antacids have the capability in aqueous media of adsorbing various organic compounds.
Accordingly, having regard to the relatively low dosage of psychosedative in comparison to antacid in the present medicaments, an insufficient resorption of ~he psychosedative would have been expected. Surprisingly, it has been found that this is not the case with the medicaments provided by the present inventionO
According to the process provided by the present invention, the medicaments aforesaid are manufactured by mixing together a psychosedative from the benzodiazepine series, from 50 to 1000 parts by weight of an antacid and from 10 to 150 parts by weight of an antiflatulent per part by weight of psychosedative and, optionally, a compatible carrier material or adjuvant or both suitable for therapeutic administration.
The mixture obtained can be brought into suitable oral dosage forms (e.g. tablets, capsules, syrups or chewing tablets) according to well-known methods. Examples of carrier materials and adjuvants are water, lactose, starch, magnesium stearate, talc and polyalkyleneglycols as well as ; flavouring substances, preservatives, stabilisers, wetting agents and emulsifiers.

i~)4'~796 The following Example illustrates the present invention:

Example Chewing tablets containing the following ingredients are manufactured:

Bromazepam 1.0 mg Aluminium hydroxide/magnesium carbonate coprecipitate500.0 mg ; Magnesium oxide 100.0 mg ; Simethicone 100.0 mg Sugar 640.0 mg D-Mannitol 600.0 mg LUVISKOL K 90 20.0 mg Magnesium stearate 20.0 mg Aroma q.s.ad. 2000.0 m~

Simethicone and magnesium oxide are stirred into an aqueous-alcoholic solution of L W ISKOL K 90. Subsequently, a mixture consisting of aluminium hydroxide/magnesium carbonate coprecipitate, D-Mannitol and a premix of bromazepam and sugar i9 added thereto with stirring. ~he moist mass is granulated, dried and sieved. A mixture of magnesium stearate and aroma material i9 added to this granulate. The mixture i5 mixed and pressed to tablets.

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Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A process for the manufacture of a medicament, which process comprises mixing together a psychosedative from the benzodiazepine series, from 50 to 1000 parts by weight of an antacid and from 10 to 15% parts by weight of an antiflatulent per part by weight of psychosedative and, optionally, a carrier material or adjuvant or both suitable for therapeutic administration.

2, A process according to claim 1, wherein chlordiazepoxide, diazepam, medazepam, bromazepam, cloxazolazepam, lorazepam, oxazepam, oxazolazepam, prazepam or temazepam is used as the psychosedative from the benzodiazepine series.

3. A process according to claim 1, wherein a salt, hydroxide or oxide of a metal of the first to third group of the periodic system or a mixture or coprecipitate thereof is used as the antacid.

4. A process according to claim 3, wherein aluminium hydroxide, aluminium glycinate, aluminium silicate, calcium silicate, calcium carbonate, magnesium oxide, magnesium hydroxide, magnesium carbonate, magnesium silicate, sodium bicarbonate or potassium carbonate is used as the antacid.

5. A process according to claim 3, wherein aluminium hydroxide/
magnesium carbonate coprecipitate or magnesium oxide or a mixture thereof is used as the antacid.

6. A process according to any one of claims 1 to 3 inclusive, wherein dimethylpolysiloxane is used as the antiflatulent.

7. A process according to any one of claims 1 to 3 inclusive, wherein bromazepam is used as the psychosedative, aluminium hydroxide/magnesium carbonate coprecipitate and magnesium oxide is used as the antacid and dimethylpolysiloxane is used as the antiflatulent.

8. A process according to claim 1, wherein from 100 to 700 parts by weight of antacid and from 15 to 125 parts by weight of antiflatulent are used per part by weight of psychosedative.

9. A process according to claim 9, wherein a unit dosage form contain-ing from about 0.5 to 5 mg of psychosedative, from 500 to 700 mg of antacid and from 75 to 125 mg of antiflatulent is manufactured.

10. A medicament containing as the active ingredients a psychosedative from the benzodiazepine series, from 50 to 1000 parts by weight of an antacid and from 10 to 150 parts by weight of an antiflatulent per part by weight of psychosedative and, optionally, a compatible carrier material or adjuvant or both suitable for therapeutic administration.

11. A medicament according to claim 10, wherein said psychosedative is chlordiazepoxide, diazepam, medazepam, bromazepam, cloxazolazepam, lorazepam, oxazepam, oxazolazepam, prazepam or temazepam.

12. A medicament according to claim 10, wherein the antacid is a salt, hydroxide or oxide of a metal of the first to third group of the periodic system or a mixture or coprecipitate thereof.

13. A medicament according to claim 12, wherein the antacid is aluminium hydroxide, aluminium glycinate, aluminium silicate, magnesium carbonate, magnesium oxide, magnesium hydroxide, magnesium silicate, sodium bicarbonate or potassium carbonate.

14. A medicament according to claim 12, wherein the antacid is aluminium hydroxide/magnesium carbonate coprecipitate or magnesium oxide or a mixture thereof.

15. A medicament according to any one of claims 10 to 12 inclusive, wherein the antiflatulent is dimethylpolysiloxane.

16. A medicament according to any one of claims 10 to 12 inclusive, wherein the psychosedative is bromazepam, the antacid is aluminium hydroxide/
magnesium carbonate coprecipitate and magnesium oxide and the antiflatulent is dimethylpolysiloxane.

17. A medicament according to claim 10 containing from 100 to 700 parts by weight of antacid and from 15 to 125 parts by weight of antiflatulent per part by weight of psychosedative.

18. A medicament according to claim 12 in unit dosage form containing from about 0.5 to 5 mg of psychosedative, from 500 to 700 mg of antacid and from 75 to 125 mg of antiflatulent.