The present invention relates generally to storage-stable sucralfate preparations and, more particularly, to sucralfate-containing compositions which retain their ability to form viscous, sticky, paste-like compositions in the presence of gastric secretions. These compositions are characterized by the inclusion of a material which helps to preserve the adhesive nature of sucralfate and the protective effects of sucralfate against acids, pepsin and bile salts. These preparations, because of this property, exhibit a sustained effect in protecting the disrupted mucosa which are characteristic of peptic ulcers, and, to a lesser degree, chronic gastritis.
An aluminum salt of sucrose sulfate ester (conventionally known as sucralfate) is an excellent ulcer curative agent with minimal side effects, and is extensively used in anti-ulcer therapy. See, for example, U.S. Pat. No. 3,432,489 which is incorporated by reference herein.
Peptic ulcers and chronic gastritis are exacerbated by the pepsin and hydrochloric acid which occur naturally in gastric juice. By virtue of its pepsin-binding and antacidic properties, sucralfate inhibits the pathogenetic activities of pepsin and hydrochloric acid in peptic ulcer and chronic gastritis, and thereby assists the natural healing process. Sucralfate also promotes revascularization and regeneration of ulcerated mucosal tissue.
Beyond these effects, the most characteristic feature of sucralfate which sets it apart from other anti-ulcer agents is its ability to selectively bind to the ulcer-affected mucosa of the stomach and duodenum rather than to normal gastrointestinal tissues, thus forming a protective coating which is impervious to pepsin and stomach acid and allowing normal healing to ensue.
Sucralfate forms a sticky paste in an acidic solution at a pH below 4.0. When administered orally, sucralfate reacts with gastric juice in the stomach to form a sticky paste which binds to the ulcer-affected part of the stomach or duodenum to exhibit a sustained effect to protect the mucosa in that part. This effect of sucralfate can be confirmed in vitro by the following procedure:
According to the Japanese Pharmacopoeia (10th ed.), 1,000 ml of artificial gastric juice (pH: ca. 1.2) is prepared from a mixture of sodium chloride (2.0 g), dilute hydrochloric acid (24 ml) and water. Sucralfate (1 g) is suspended in 10 ml of the gastric juice in a test tube, and immediately thereafter, sucralfate forms a sticky paste which adheres to the inner surface of the test tube as if sucralfate administered orally contacted acid in the stomach and formed a viscous paste.
In the course of these in vitro studies on sucralfate, it has unexpectedly been found that an aqueous suspension of sucralfate or a solid preparation thereof placed under hot and humid conditions loses partly, or entirely, the most characteristic feature of sucralfate (ability to form a sticky paste in the artificial gastric juice) although its other properties remain substantially unchanged. In particular, this phenomemon occurs in the aqueous suspension in about 15 to 20 days after its preparation, and sucralfate particles remain suspended even if the suspension is mixed with the artificial gastric juice. Animal experiments were conducted with rats in which ulcers were artificially induced, and confirmed that sucralfate preparations with reduced ability to form a viscous paste were not highly effective in protecting the ulcer-affected mucosa from attacking factors.