(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 8 April 2010 (08.04.2010) WO 2010/038241 A2 (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, A61K 9/48 (2006.01) A61K 47/36 (2006.01) CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, A61K 31/4439 (2006.01) A61P 1/04 (2006.01) DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (21) International Application Number: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, PCT/IN2009/000540 ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, (22) International Filing Date: NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, 30 September 2009 (30.09.2009) SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of regional protection available): ARIPO (BW, GH, (30) Priority Data: GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, 2284/DEL/2008 30 September 2008 (30.09.2008) IN ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, (71) Applicant (for all designated States except US): ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, PANACEA BIOTEC LIMITED [IN/IN]; Panacea MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, Biotec Ltd., B-I, Extn. /A- 27 Mohan Co-operative, Indl. TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, Estate, Mathura Road, New Delhi 110 044 (IN). ML, MR, NE, SN, TD, TG). (72) Inventors; and Declarations under Rule 4.17: (75) Inventors/Applicants (for US only): JAIN, Rajesh — as to the identity of the inventor (Rule 4.17(ϊ)) [IN/IN]; B-I Extn. / A- 27 Mohan Co-operative, Industri al Estate, Mathura Road, New Delhi 110 044 (IN). — as to applicant's entitlement to apply for and be granted SINGH, Sukhjeet [IN/IN]; B-I Extn. / A- 27, Mohan a patent (Rule 4.1 7(H)) Co-operative, Industrial Estate, Mathura Road, New Delhi — of inventorship (Rule 4.1 7(iv)) 110 044 (IN). Published: (74) Agent: GUPTA, Bhartee; B-I Extn. / A- 27, Mohan Co operative, Industrial Estate, Mathura Road, New Delhi — without international search report and to be republished 110 044 (IN). upon receipt of that report (Rule 48.2(g)) (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (54) Title: PHARMACEUTICAL COMPOSITIONS COMPRISING OF PROTON PUMP INHIBITOR, PROKINETIC AGENT AND ALGINIC ACID (57) Abstract: Oral pharmaceutical compositions and process for preparing compositions comprising at least one gastric acid sup pressing agent, at least one prokinetic agent and at least one alginic acid optionally with pharmaceutically acceptable excipients are provided; such that the gastric acid suppressing agent is present in a delayed release form, prokinetic agent is present in a bi- modal release form such as an immediate release form, and a delayed release form to provide a dose with a lag time form and al ginic acid is present in an immediate release form. The said compositions are useful in the treatment of gastric acid related disor ders such as gastro esophageal reflux disease, reflux esophagitis, peptic ulcer, gastric ulcer, heartburn, sour stomach, acid inges tion, upset stomach and/or pain associated with heartburn, sour stomach and acid ingestion, bloating, fullness, dyspepsia, noctur nal heartburn, disorders not manifested by the presence of ulcerations in the gastric mucosa, including chronic active or atrophic gastritis, and Zollinger-Ellison syndrome. PHARMACEUTICAL COMPOSITIONS COMPRISING OF PROTON PUMP INHIBITOR, PROKINETIC AGENT AND ALGINIC ACID FIELD OF THE INVENTION The present invention relates to oral pharmaceutical compositions and process for preparing compositions comprising at least one gastric acid suppressing agent, at least one prokinetic agent and at least one alginic acid optionally with pharmaceutically acceptable excipients; such that the gastric acid suppressing agent is present in a delayed release form, prokinetic agent is present in a bimodal release form such as an immediate release form, and a delayed release form to provide a dose with a lag time form and alginic acid is present in an immediate release form. The said compositions are useful in the treatment of gastric acid related disorders such as gastro esophageal reflux disease, reflux esophagitis, peptic ulcer, gastric ulcer, heartburn, sour stomach, acid ingestion, upset stomach and/or pain associated with heartburn, sour stomach and acid ingestion, bloating, fullness, dyspepsia, nocturnal heartburn, disorders not manifested by the presence of ulcerations in the gastric mucosa, including chronic active or atrophic gastritis, and Zollinger-Ellison syndrome. BACKGROUND OF THE INVENTION Gastro esophageal reflux disease (GERD), reflux esophagitis, peptic ulcer, gastric ulcer and other gastric acid related disorders are disorders having a pathogenesis related to reduced gastric motility and release of excessive gastric acid. Apart from lifestyle modifications, GERD and gastric ulcer have been successfully treated with a range of gastric acid inhibitors, such as ranitidine and omeprazole, which are acid-suppressing agents. Stimulation of gastric motility has been proposed to accelerate the healing of gastric ulcer. Prokinetic agents, such as domperidone, are known to enhance gastrointestinal motility and prevent duodenogastric reflux, and are widely used to treat GERD. Proton pump inhibitors, H2 receptor antagonists and prokinetic agents have been used in combination to treat gastric ulcer and other related disorders. Proton pump inhibitors (PPIs) are a class of acid-labile pharmaceutical compounds that I block gastric acid secretion pathways. Exemplary proton pump inhibitors include, omeprazole (Prilosec.RTM.), lansoprazole (Prevacid.RTM.), esomeprazole (Nexium.RTM.), rabeprazole (Aciphex.RTM.), paπtoprazole (Protonix.RTM.), pariprazole, tenatoprazole, and leminoprazole. The drugs of this class suppress gastrointestinal acid secretion by the specific inhibition of the H.sup.+/K.sup.+-ATPase enzyme system (proton pump) at the secretory surface of the gastrointestinal parietal cell. Most proton pump inhibitors are susceptible to acid degradation and, as such, are rapidly destroyed in an acidic pH environment in the stomach. Therefore, proton pump inhibitors are often administered as enteric-coated dosage forms in order to permit release of the drug in the duodenum after having passed through the stomach. Prilosec.RTM. (omeprazole) is formulated as enteric-coated granules in gelatin capsules. Prevacid.RTM. (lansoprazole) is available as enteric-coated granules in gelatin capsules, and as enteric-coated microspheres for use as a liquid suspension. Nexium.RTM. (esomeprazole magnesium) is enteric-coated granules in gelatin capsules. Proton pump inhibitors are typically prescribed for short-term treatment of active duodenal ulcers, gastrointestinal ulcers, gastroesophageal reflux disease (GERD), severe erosive esophagitis, poorly responsive symptomatic GERD, and pathological hypersecretory conditions such as Zollinger Ellison syndrome. These above-listed conditions commonly arise in healthy or critically ill patients of all ages, and may be accompanied by significant upper gastrointestinal bleeding. H2-receptor antagonists are frequently employed to treat disorders linked to the hypersecretion of gastric acid, for example the treatment of gastric ulcers, as they inhibit the secretion of gastric acid. Histamine H2-receptor antagonists may be chosen from a series of well-known products such as cimetidine, ranitidine, famotidine, etc. Prokinetic agents may be prescribed in the treatment of various gastrointestinal diseases, such as gastroesophageal reflux disease (GERD), inflammatory bowel disease, or to treat primary gastrointestinal motility disorders, such as diffuse esophageal spasm or irritable bowel syndrome. Motility disorders of the gastrointestinal tract may be caused by neural, muscular or receptor damage dysfunction. Prokinetic agents would be useful in concomitant therapy with proton pump inhibitors to treat patients with GERD, erosive esophagitis or functional dyspepsia. PPI and prokinetic agent combinations increase the tone of the lower esophageal sphincter, decrease the number of transient lower esophageal relaxations, and increase gastric emptying while the proton pump inhibitor administered decreases the volume of gastric juice available for reflux into the esophagus and increases the pH so Jhat refluxed gastric contents are much less injurious to the esophageal mucosa. Alginic acid and its salts with sodium and potassium bicarbonate have shown that, after entering the stomach environment they form a viscous suspension or a gel exerting protecting activity over gastric mucosa. The scientific and patent literature on its activity is wide. Alginates may be used alone in the treatment of heartburn. They have a short duration of action but are seen as inexpensive and safe. Alginates further give some mechanical protection against reflux or gastric acid into the esophagus. Sodium alginate forms a 'raft' which floats to the top of the stomach, forming a barrier between the acid and the oesophagus, thus preventing acid refiuxing into the oesophagus and protecting the mucosa from further irritation. The main advantage of alginates is that they provide fast relief of symptoms. Esomeprazole magnesium is bis (5-methoxy-2-[(S)-[(4-methoxy-3,5-dimethyl-2- pyridinyl) methyl]sulf ϊnyl]-lH-benzimidazole-l-yl) magnesium trihydrate, a compound that inhibits gastric acid secretion. Esomeprazole is the S-isomer of omeprazole, which is a mixture of the S- and R- isomers. Its molecular formula is (C 17H 18NsO S)2 Mg.3 H O with molecular weight of 767.2 as a trihydrate and 713.1 on an anhydrous basis. Metoclopramide is 4-amino-5-chloro-N-(2-(diethylamino) ethyl)-2-methoxybenzamide and a potent dopamine receptor antagonist used for its antiemetic and prokinetic properties.