Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1996-01-29
1997-08-26
Henley, III, Raymond
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
424686, 424687, 424692, A61K 31715, A61K 3310, A61K 3308
Patent
active
056611374
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP94/02477 filed Jul. 27, 1994.
FIELD OF THE INVENTION
The present invention relates to antacid pharmaceutical compositions in the form of suspensions containing sucralfate gel as an active ingredient combined with suitable excipients and/or diluents.
STATE OF THE ART
Sucralfate, i.e. the complex of sulphated sucrose and aluminium hydroxide, is an antiulcer drug. It exerts an inhibitory action against pepsin and, as more recently found, a cytoprotective action. In the solid state, sucralfate reacts with the acids of the stomach giving a tacky mucosa-adhesive substance, denominated paste. Said tacky substance is deemed essential to secure the antiulcer activity of sucralfate: it adheres to the ulcers and maintains the pH of the gastric microenvironment at ideal values for pepsin activity inhibition.
Due to sucralfate basicity, 1 g of product can neutralize approx. 13 mEq hydrogen ions.
On addition to 0.1N hydrochloric acid, sucralfate in powder form rapidly becomes tacky and adhesive, and yields approx. 10% of its antacid power within 2 to 3 minutes. After said initial yield, even if the reaction medium is maintained under vigorous stirring, the reaction with the acid becomes very slow as it is hindered by the paste viscosity.
Therefore, although sucralfate is suitable for the treatment of ulcers, it cannot be used as an antiacid.
In fact, as well known to those skilled in the art, the therapeutic activity of antacid preparation depends not only on its absolute acidity neutralization, but also and especially on its acidity neutralization rate in the gastric environment.
Advanced pharmacopoeias state that the therapeutic activity of an antacid preparation is a function of two basic parameters: reaction rate and neutralization duration.
The first parameter, i.e. the reaction rate, concerns acidity neutralization for a fast relief of the heartburn sensation (pyrosis) generally accompanying gastric hyperacidity; the second parameter, i.e. neutralization duration, concerns the development of a buffer action maintaining for an appropriate time the gastric lumen pH above the value at which said painful sensation is no more felt.
As concerns the first parameter, sucralfate exerts a poor action: paste formation considerably slows down its reactivity and, therefore, a pH value compatible with pyrosis suppression cannot be obtained. As concerns the second parameter, sucralfate is unable to maintain the pH value reached for an appropriate time: theoretically it can maintain the gastric environment buffered, but in fact, against a continuous secretion of the gastric juice, it does not exert any buffering action due to the low reactivity of the paste that formed.
It follows that sucralfate can exert an antacid action only if chemically transformed into a specific antiacid product, as disclosed in EP 437406. Therefore, sucralfate powder cannot constitute an efficacious active ingredient of an antacid, preparation.
EP 286978 by the Applicant discloses sucralfate in the form of gel, with particles dimensional distribution practically at the limit of colloidal size, which secures a very high specific surface of the product.
Sucralfate gel exerts a more potent antiulcer action than the powder form of general use and, when contacted with acids, does not form the paste already mentioned. The higher activity of the product was proved to result from its specific ability to adhere to the mucosa, i.e. from the bioadhesion, taking place without any intervention of the acids.
The sucralfate gel aqueous suspension shows unique thixotropic-type theological properties revealing a considerable surface activity of the particles, which very easily gives rise to interactions both with one another and with the biological substrates.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates the change of pH on addition of 0.5N HCl to 1 g of sucralfate gel and, respectively, sucralfate powder at 25.degree. C.
FIG. 2 shows the antacid, effectiveness by Rosset-Rice's test and the results obtained with antacid
REFERENCES:
patent: 5246697 (1993-09-01), Conte et al.
patent: 5321013 (1994-06-01), Zagnoli et al.
"Avery's Drug Treatment", T.M. Speight Ed., pp. 742-743. 1987.
J.E.F. Reynolds-Martindale, "The Extra Pharmacopeia" 29th Edition, p. 1108, 07-m (1989).
Henley III Raymond
Laboratorio Italiano Biochimico Farmaceutico Lisapharma S.p.A.
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