MXPA96003747A - Antitus composition - Google Patents

Abstract

The present invention relates to an oral antitussive pharmaceutical composition, comprising from about 3.0 mg of benzydamine or an equivalent amount of its hydrochloride or hydrobromide salt and about 7.5 mg of dextromethorphan or an equivalent amount of its hydrobromide or hydrate salt. Bromhydrate

Description

ANTITUSIVE COMPOSITION DESCRIPTION OF THE INVENTION This invention relates to an antitussive composition. More particularly, this invention relates to an oral antitussive composition, characterized in that it comprises a centrally acting antitussive or a pharmaceutically acceptable salt thereof, and benzydamine or a pharmaceutically acceptable salt thereof. Cough is a useful physiological action to release the respiratory tract of foreign substances and excess secretions. However, in some cases, the cough performs not useful purposes, rather irritates the patient or prevents the patient from resting or sleeping. This leads to the need to administer a drug capable of reducing the recurrence and / or severity of cough. Among the various drugs that reduce cough, some act on the central nervous system. Examples of such antitussives are: codeine, dextromethorphan, dihydrocodeine, dimormorphan, noscapine, levopropoxyphene, napsylate, carbetapentane, caramiphen, clofedianol, glaucine, benzonatate, hydrocodone, and hydromorphone. The most commonly used are: codeine, dextromethorphan, dihydrocodeine, dimemorfan and noscapine. Dextromethorphan is a particularly significant example of a centrally acting, non-narcotic antitussive (The Merck Index, 9th ed., 1976, page 1289, No. 8116). The average dose of dextromethorphan hydrobromide, given to adults, is 15 to 30 mg, 3 to 4 times a day (Goodman &Gilman - "Le Basi Farmacologiche della Terapia" - 8th Italian edition, Zanichelli - Bologna). It is available in lozenges, tablets, syrups and drops, alone or in association with balsamic expectorant products. Benzydamine (The Merck Index, 9th Edition, 1976, page 147, No. 1136) was first described by US-3 318 905, which refers to a group of products that have analgesic, anti-inflammatory and relaxant activity. muscles It was widely used in the therapy of the human being as hydrochloride. As far as the systemic route is concerned, it is mainly used as an anti-inflammatory and analgesic agent, by topical route, however, it is mainly used in those pathologies that involve local inflammation such as, for example, myalgia, tendonitis, vulvovaginitis, gingivitis, stomatitis. , inflammation of the mucosa of the oral cavity, and the like. Now, it has unexpectedly been found that benzydamine and its pharmaceutically acceptable acid addition salt are capable of shortening the time of onset of the action of centrally acting antitussives on the peripheral stimulus of cough in particular pathologies compared to the antitussive alone. This unexpected effect has been proven by clinical analyzes in humans. Therefore, it is a first object of this invention to provide an oral antitussive pharmaceutical composition, characterized in that: it allows a significant contact of its components with the membranes of the mucosa of the oral cavity, and comprises a centrally acting antitussive or a salt pharmaceutically acceptable thereof and benzydamine or a pharmaceutically acceptable acid addition salt thereof. For example, dextromethorphan alone performs its action in 20-30 minutes (Matthys, B. Bleiche et al., J. Int. Med. Res., 1_1_, 92-1 00, 1 983). However, when administered in association with benzydamine or its pharmaceutically acceptable acid addition salt, in a pharmaceutical dosage form, which allows significant contact of its components with the mucosal membranes of the oral cavity, it reduces the symptom of the cough in a much shorter time, that is to say in a few minutes. Examples of suitable pharmaceutical dosage forms, which allow significant contact of their components with the mucosal membranes of the oral cavity, are pills, sweets, chewable tablets and chewing gums. In addition to benzydamine or an acid addition salt of the same, such as hydrochloride, and a centrally acting antitussive or a pharmaceutically acceptable salt thereof, the compositions of this invention comprise a diluent or solid or fluid inert carrier and , optionally, other additives suitable for pharmaceutical use, and are prepared by conventional techniques.

Examples of suitable additives are sweeteners, flavors, and colorants. In the composition of this invention, the effective dose of benzydamine and a centrally acting antitussive will vary depending on several factors that are well known to those skilled in the art, such as the antitussive used, individual response, age and general health condition of the patient. However, in general, the composition of this invention will comprise an amount of a central action antitussive from 0.5 to twice the normal dose thereof, or the equivalent amount of a pharmaceutically acceptable salt thereof. In this description, the term "normal dose" is intended to represent the effective dose that is usually administered by the oral route for each individual, centrally acting antitussive. For example, in the case of dextromethorphan, the effective dose varies from 5 to 30 mg per administration, depending on whether the treatment (1-6 times per day) is for children or adults. In some cases, however, individual doses of 60 mg were also administered (Goodman &Gilman, 7th Italian, page 486). As far as benzydamine is concerned, the amount that proved to be able to reduce the time of onset of action of the central action antitussive on the peripheral stimulus of cough, varies depending on the specific antitussive and the pharmaceutical dosage form used. . Typically, as for benzydamine, the pharmaceutical compositions of this invention will comprise: (a) a weight amount of 1/200 to two times the amount by weight of the centrally acting antitussive, or (b) the equivalent amount of a salt pharmaceutically acceptable addition acid thereof. A first preferred composition of this invention comprises 0.15 to 10 mg of benzydamine and 5 to 30 mg of dextromethorphan or equivalent amounts of a pharmaceutically acceptable salt thereof. Finally, the pharmaceutical compositions of this invention can also comprise other active ingredients, whose utility, together with the centrally acting antitussives, is known. Typical examples of said active ingredients are antihistamines and balsamic agents. The following examples are intended to illustrate this invention without, however, limiting it.

EXAMPLE 1 Chewable Tablets Each 1.37 g tablet contains: Benzydamine Hydrochloride 3.0 mg Bromhydrate, dextromethorphan hydrate 7.5 Mannitol 1121 5"Maltol 200.0" Magnesium trisilicate 67.5 Magnesium stearate 15.5" Ammonium glycyrrhizinate 15.0"Aspartame 15.0" Balsamic flavor 15.0" Ester palmitic-stearic glycerol 10.0" This tablet was prepared by the direct compression method; the active ingredients were premixed to ensure uniformity of the content in the finished product. The maltol and part of the mannitol were placed in a Zanchetta ™ mixer. Benzamine hydrochloride and dextromethorphan hydrobromide monohydrate, adsorbed at 10% on magnesium trisilicate, were placed in a smaller mixer and then the balsamic flavor, aspartame, ammonium glycyrrhizinate, and the remaining mannitol were added. The mixture was combined for approximately 15 minutes and then transferred to the blender containing mannitol and maltol.

Then, the magnesium stearate and the palmitic-stearic glycerol ester were added and mixed until homogeneous for about 30 minutes. The mixture was compressed by means of a rotating machine, equipped with punches (20.5 x 1 1 .5 mm).

EXAMPLE 2 Sweets Each 5 g sweet contains: Benzydamine Hydrochloride 3.0 mg Dextromethorphan Bromhydrate 7.5 Lycasin 80/55 4165.0" Gum arabic 79.0" Manitol 725.0"Natural flavors 20.3" Natural colorants 0.2 EXAMPLE 3 Sweets Each 5 g sweet contains: Benzydamine Hydrochloride 3.0 mg Dextromethorphan Bromhydrate 7.5" Sucrose 3052.5"Glucose 1920.0" Mint 12.0" Menthol 4.8 Natural colorants 0.2

Claims (8)

1 , . An antitussive, pharmaceutical, oral composition characterized in that it allows a significant contact of its components with the mucosal membranes of the oral cavity, and comprises a centrally acting antitussive or a pharmaceutically acceptable salt thereof and benzydamine or an acid salt of pharmaceutically acceptable addition thereof.

2. A composition according to claim 1, characterized in that it is in the form of pills, sweets, chewable tablets, or chewing gums.

3. A composition according to any of claims 1 and 2, characterized in that it comprises from 0.5 to twice the normal dose of an antitussive, central action, selected from the group comprising, codeine, dextromethorphan, dihydrocodeine, dimemorfan, noscapine , levopropoxyphene, napsylate, carbetapentane, caramiphen, chlophedianol, diphenhydramine, glaucine, benzonatate, hydrocodone, hydromorphone, and the pharmaceutically acceptable salt thereof.

4. A composition according to any of claims 1 and 3, characterized in that it comprises an amount of benzidramine of 1/200 to two times the amount by weight of the central action antitussive or the equivalent amount of an acid addition salt pharmaceutically acceptable of it

5. - A composition according to claim 1, characterized in that it comprises 0.15 to 10 mg of benzydamine and 5 to 30 mg of dextromethorphan or equivalent amounts of its pharmaceutically acceptable salt.

6. A composition according to claim 5, characterized in that the pharmaceutically acceptable salt of benzydamine is hydrochloride.

7. A composition according to claim 5 or 6, characterized in that the pharmaceutically acceptable salt of dextromethorphan is hydrobromide.

8. A composition according to claim 5 or 6, characterized in that the pharmaceutically acceptable salt of dextromethorphan is hydrate-hydrobromide.