Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Patent
1997-02-13
2000-10-17
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
424469, 424470, 424475, 424490, 424482, 424480, 424460, 514925, A61K 922, A61K 930, A61K 926, A61K 950
Patent
active
061327719
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention is related to new oral pharmaceutical preparations especially for use in the prevention and treatment of disorders associated with gastro oesophageal reflux. The present preparations comprise a gastric acid suppressing agent, such as a proton pump inhibitor, in combination with one or more prokinetic agents in a new fixed unit dosage form, especially a tablet. Furthermore, the present invention refers to a method for the manufacture of such preparations and the use of such preparations in medicine, especially in the treatment of gastro oesophageal reflux diseases and other gastrointestinal disorders.
BACKGROUND OF THE INVENTION
Gastro oesophageal reflux disease (GORD) is among the most common disorders seen by gastroenterologists and general practicians. The wide diversity of symptoms and disease severity produced by acid reflux has led to the need for more individualized treatment strategies. Therapeutic agents effective in the treatment of GORD include gastric acid suppressing agents, such as H.sub.2 receptor antagonists, proton pump inhibitors, other agents of interest are antacids/alginates and prokinetic agents. These agents can be distinguished by their mechanisms of action, safety profile, pharmacokinetics and indications.
Antacids and alginates are still widely used. They have a short duration of action but are seen as inexpensive and safe. They do not provide a layterm symptom resolution of GORD.
H.sub.2 receptor antagonists are widely prescribed for GORD. Their higher cost has been compensated by the clinical results obtained both in terms of symptom relief and healing. These advantages have been related to their mode of action, which offered more potent and longer duration of effect on gastric acidity.
Proton pump inhibitors, such as omeprazole, are rapidly taking share from H.sub.2 receptor antagonists, particularly in reflux oesophagitis. Omeprazole is known to offer significant gain over H.sub.2 receptor antagonists in terms of symptom resolution, healing and prevention of relapse for reflux oesophagitis.
Prokinetic agents of the first generation, e.g. bethanecol, stimulates cholinergic receptors, and of the second generation, e.g. domperidone and metoclopramide, blocks effects of endogenous dopamine in the gut. The results of double-blind placebo controlled trials in GORD patients have been conflicting. The action of the third generation of prokinetic agents, such as substituted benzamides, e.g. cisapride and mosapride derives primarily, but not exclusively, from facilitating acetylcholine release from neurones of the myenteric plexus via stimulation of 5-HT4 receptors. The efficacy of orally administered benzamides, such as cisapride, in patients with GORD and reflux oesophagitis has been studied and a superior effect in alleviating gastro-oesophageal symptoms and healing low grade oesophagitis (non circumferential erosion) has been shown in most studies.
Patients with severe symptoms, severe mucosal damage or both are almost always treated with proton pump inhibitors for profound and long-term control of gastric acid secretion. Patients with mild symptoms and limited mucosal damage respond best to H2-receptor antagonist, prokinetic agents or proton pump inhibitors.
A combination therapy of a prokinetic agent and a gastric acid lowering compound is rational and was shown more effective than mono therapy apart from full dose of proton pump inhibitors. Administration of cisapride and ranitidine was shown to further lower the exposure of the oesophagus to acid(s) (Inauen W et al. Gut 1993; 34: 1025-1031). Such a therapy was also shown to improve healing rates (de Boer WA et al. Aliment Pharmacol Ther 1994; 8: 147-157). WO 95/01803 describes a pharmaceutical composition of famitidine, cisapride and optionally simethicone in the treatment of gastrointestinal distress.
Maintenance therapy is often necessary to prevent recurrent symptoms and oesophagitis. Recently a combination therapy combining an acid-suppressing medication with a prokinetic (cisa
REFERENCES:
patent: 4786505 (1988-11-01), Lovgren et al.
patent: 5330982 (1994-07-01), Tyers
patent: 5753265 (1998-05-01), Bergstrand et al.
patent: 5817338 (1998-10-01), Bergstrand et al.
Vigneri et al. 1995 "A comparison of five maintenance therapies . . ." The N.E.J. of Medicine 333: 1106-1110, Oct. 26, 1995.
Boer et al. 1994 "Review article: drug therapy for reflux oesophagitis" Aliment Pharmacol. Ther. 8: 147-157.
Inauen et al. 1993 "Effects of ranitidine and cisapride on acid reflux" Gut 34: 1025-1031.
Depui Helene
Hallgren Agneta
Astrazeneca AB
Page Thurman K.
Seidleck Brian K
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