DOCSLIB.ORG

Wo 2010/038241 A2

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Wo 2010/038241 A2 (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.
Load more

Recommended publications
  • Granisetron "Vianex"
    EU‐RISK MANAGEMENT PLAN GRANISETRON VIANEX® 1 MG/ML, SOLUTION FOR INJECTION/ INFUSION precautionary measure, breast‐feeding should not be advised during treatment with Granisetron “Vianex”. Legal Status: Prescription only product. VI.2 Elements for a public summary VI.2.1 Overview of disease epidemiology Nausea and vomiting associated with chemotherapy and radiotheraphy: One of the most distressing symptoms for patients undergoing both surgery and chemotherapy is nausea and vomiting. These symptoms have a significant impact on quality of life and can lead to malnutrition, inability to respond to treatment and an increased length of hospitalization. Emesis is more commonly associated with chemotherapeutic agents; however, radiation‐induced nausea and vomiting (RINV) can affect a significant proportion of patients, depending on the treated area, dose fractionation, and volume of radiotherapy. The relative risk for developing nausea and vomiting with chemotherapy ranges from 30 to 90% and is dependent upon the chemotherapeutic agent used. Relative risk for nausea and vomiting with radiation therapy is approximately 40%.2,3,4,5 Post‐operative nausea and vomiting Postoperative nausea and vomiting (PONV) is a major source of patient dissatisfaction and is the leading cause of discharge delays and unanticipated postsurgical hospital admissions. In the absence of pharmacological treatment, the rate of PONV is approximately 30% in general population, and can be as high as 70% in patients at highest risk. Several risk factors as surgery type, female gender, non‐smoker status, history of postoperative nausea and vomiting or motion sickness and post‐operative opioid use have been acknowledged. Additionally, post‐ operative vomiting (POV) occurs twice as frequently in children as in adults, increasing until puberty and then decreasing to adult incidence rates.
    [Show full text]
  • Therapeutic Class Overview Irritable Bowel Syndrome Agents
    Therapeutic Class Overview Irritable Bowel Syndrome Agents Therapeutic Class Overview/Summary: This review will focus on agents used for the treatment of Irritable Bowel Syndrome (IBS).1-5 IBS is a gastrointestinal syndrome characterized primarily by non-specific chronic abdominal pain, usually described as a cramp-like sensation, and abnormal bowel habits, either constipation or diarrhea, in which there is no organic cause. Other common gastrointestinal symptoms may include gastroesophageal reflux, dysphagia, early satiety, intermittent dyspepsia and nausea. Patients may also experience a wide range of non-gastrointestinal symptoms. Some notable examples include sexual dysfunction, dysmenorrhea, dyspareunia, increased urinary frequency/urgency and fibromyalgia-like symptoms.6 IBS is defined by one of four subtypes. IBS with constipation (IBS-C) is the presence of hard or lumpy stools with ≥25% of bowel movements and loose or watery stools with <25% of bowel movements. When IBS is associated with diarrhea (IBS-D) loose or watery stools are present with ≥25% of bowel movements and hard or lumpy stools are present with <25% of bowel movements. Mixed IBS (IBS-M) is defined as the presence of hard or lumpy stools with ≥25% and loose or water stools with ≥25% of bowel movements. Final subtype, or unsubtyped, is all other cases of IBS that do not fall into the other classes. Pharmacological therapy for IBS depends on subtype.7 While several over-the-counter or off-label prescription agents are used for the treatment of IBS, there are currently only two agents approved by the Food and Drug Administration (FDA) for the treatment of IBS-C and three agents approved by the FDA for IBS-D.
    [Show full text]
  • Novel Formulations for Treatment of Migraine
    (19) TZZ _T (11) EP 2 756 756 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 23.07.2014 Bulletin 2014/30 A01N 43/42 (2006.01) A61K 31/44 (2006.01) (21) Application number: 14165112.5 (22) Date of filing: 24.04.2009 (84) Designated Contracting States: • Turanin, John AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Emeryville, CA California 94608 (US) HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL • Hawley, Roger PT RO SE SI SK TR Emeryville, CA California 94608 (US) • Schuster, Jeffrey, A. (30) Priority: 28.04.2008 US 48463 Bolinas, CA California 94924 (US) (62) Document number(s) of the earlier application(s) in (74) Representative: Duxbury, Stephen et al accordance with Art. 76 EPC: Arnold & Siedsma 09739139.5 / 2 273 880 Pettenkoferstrasse 37 80336 München (DE) (71) Applicant: Zogenix, Inc. Emeryville CA 94608 (US) Remarks: This application was filed on 17-04-2014 as a (72) Inventors: divisional application to the application mentioned • Farr, Stephen J. under INID code 62. Orinda, CA California 94563 (US) (54) Novel formulations for treatment of migraine (57) Systems and methods are described for treating Systems that are self contained, portable, prefilled, and un-met medical needs in migraine and related conditions simple to self administer at the onset of a migraine attack such as cluster headache. Included are treatments that are disclosed, and preferably include a needle-free in- are both rapid onset and long acting, which include sus- jector and a high viscosity formulation, to eliminate such tained release formulations, and combination products, issues as fear of self administration with needles, and Also included are treatments for multiple symptoms of needle stick and cross contamination.
    [Show full text]
  • 5-HT3 Receptor Antagonists in Neurologic and Neuropsychiatric Disorders: the Iceberg Still Lies Beneath the Surface
    1521-0081/71/3/383–412$35.00 https://doi.org/10.1124/pr.118.015487 PHARMACOLOGICAL REVIEWS Pharmacol Rev 71:383–412, July 2019 Copyright © 2019 by The Author(s) This is an open access article distributed under the CC BY-NC Attribution 4.0 International license. ASSOCIATE EDITOR: JEFFREY M. WITKIN 5-HT3 Receptor Antagonists in Neurologic and Neuropsychiatric Disorders: The Iceberg Still Lies beneath the Surface Gohar Fakhfouri,1 Reza Rahimian,1 Jonas Dyhrfjeld-Johnsen, Mohammad Reza Zirak, and Jean-Martin Beaulieu Department of Psychiatry and Neuroscience, Faculty of Medicine, CERVO Brain Research Centre, Laval University, Quebec, Quebec, Canada (G.F., R.R.); Sensorion SA, Montpellier, France (J.D.-J.); Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran (M.R.Z.); and Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada (J.-M.B.) Abstract. ....................................................................................384 I. Introduction. ..............................................................................384 II. 5-HT3 Receptor Structure, Distribution, and Ligands.........................................384 A. 5-HT3 Receptor Agonists .................................................................385 B. 5-HT3 Receptor Antagonists. ............................................................385 Downloaded from 1. 5-HT3 Receptor Competitive Antagonists..............................................385 2. 5-HT3 Receptor
    [Show full text]
  • Gastroparesis: 2014
    GASTROINTESTINAL MOTILITY AND FUNCTIONAL BOWEL DISORDERS, SERIES #1 Richard W. McCallum, MD, FACP, FRACP (Aust), FACG Status of Pharmacologic Management of Gastroparesis: 2014 Richard W. McCallum Joseph Sunny, Jr. Gastroparesis is characterized by delayed gastric emptying without mechanical obstruction of the gastric outlet or small intestine. The main etiologies are diabetes, idiopathic and post- gastric and esophageal surgical settings. The management of gastroparesis is challenging due to a limited number of medications and patients often have symptoms, which are refractory to available medications. This article reviews current treatment options for gastroparesis including adverse events and limitations as well as future directions in pharmacologic research. INTRODUCTION astroparesis is a syndrome characterized by documented gastroparesis are increasing.2 Physicians delayed emptying of gastric contents without have both medical and surgical approaches for these Gmechanical obstruction of the stomach, pylorus or patients (See Figure 1). Medical therapy includes both small bowel. Patients can present with nausea, vomiting, prokinetics and antiemetics (See Table 1 and Table 2). postprandial fullness, early satiety, pressure, fullness The gastroparesis population will grow as diabetes and abdominal distension. In addition, abdominal pain increases and new therapies will be required. What located in the epigastrium, and distinguished from the do we know about the size of the gastroparetic term discomfort, is increasingly being recognized population? According to a study from the Mayo Clinic as an important symptom. The main etiologies of group surveying Olmsted County in Minnesota, the gastroparesis are diabetes, idiopathic, and post gastric risk of gastroparesis in Type 1 diabetes mellitus was and esophageal surgeries.1 Hospitalizations from significantly greater than for Type 2.
    [Show full text]
  • 8-GI Drugs Final
    Gastrointestinal Drugs Subcommittee: Prozialeck, Walter (Chair) [email protected] Escher, Emanuel [email protected] Garrison, James C. [email protected] Henry, Matthew, [email protected] Weber, Donna R [email protected] Recommended Curriculum Equivalent: 1.5 h Acid Reducers and Drugs for the Treatment of Peptic Ulcer Disease Proton pump inhibitors First generation Second generation OMEPRAZOLE ESOMEPRAZOLE LANSOPRAZOLE PANTOPRAZOLE RABEPRAZOLE Learning Objectives Physiology and pathophysiology Describe the synthesis and mechanism of H+ secretion by the parietal cells Mechanism of action Describe the mechanism of action of proton pump inhibitors and why they are selective for the parietal cell proton pump. Actions on organ systems Describe the pharmacological effects of the drugs on gastric function. Are there effects on other organ systems? Pharmacokinetics Describe the pharmacokinetics of proton pump inhibitors? Are there significant differences among the different drugs in this class? Adverse effects, drug interactions and contraindications Describe the principal adverse effects of proton pump inhibitors. Describe the clinically important drug interactions of proton pump inhibitors. Describe the principal contraindications of proton pump inhibitors. Therapeutic uses Describe the current therapeutic uses of proton pump inhibitors. 1 Clinical Pharmacology Omeprazole is perceived to be the most potent of this drug class in inhibiting CYP2C19 activity and is proposed to have potential drug interactions with other drugs metabolized by this P450 isoform. Concern has been raised about potential inhibition of clopidogrel activation in patients taking both drugs concurrently. Current consensus is that in such patients clopidogrel with pantoprazole may be a safer choice to reduce the probability of a drug interaction involving CYP2C19.
    [Show full text]
  • The Use of Stems in the Selection of International Nonproprietary Names (INN) for Pharmaceutical Substances
    WHO/PSM/QSM/2006.3 The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances 2006 Programme on International Nonproprietary Names (INN) Quality Assurance and Safety: Medicines Medicines Policy and Standards The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 © World Health Organization 2006 All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; e-mail: [email protected]). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.
    [Show full text]
  • CISAPRIDE (Veterinary—Systemic)
    CISAPRIDE (Veterinary—Systemic) There are no human- or veterinary-labeled commercial ELUS,CANDelayed gastric emptying (treatment)EL; or cisapride products in the United States or Canada. ELUS,CANSmall bowel motility disorders (treatment)EL— Although no feline studies are available, the Category: Gastrointestinal emptying adjunct; documented effects of cisapride in healthy dogs and peristaltic stimulant. other animals suggest it may have efficacy in disorders that benefit from stimulation of gastric, Indications small intestinal, or colonic motility and from Note: Cisapride is not specifically approved for shortened transit time in cats (Evidence rating: B- {R-2; 4-7; 21-24} veterinary use. In other USP information 2). monographs, the ELUS and ELCAN designations refer to uses that are not included in U.S. and Canadian Dogs product labeling; however, in this monograph Potentially effective they reflect the lack of commercial product ELUS,CANGastroesophageal reflux (treatment)EL; availability in the countries indicated. See also the ELUS,CANDelayed gastric emptying (treatment)EL; Regulatory Considerations section below in this ELUS,CANSmall bowel motility disorders (treatment)EL; or monograph. US,CAN EL Colonic motility disorders (treatment)EL — Classification as Accepted, Potentially effective, Although no studies of clinical disease states are or Unaccepted is an evaluation of reasonable use available, studies of the effects of cisapride in that considers clinical circumstances, including healthy dogs suggest it may have efficacy in the availability of other therapies. The quality of disorders that benefit from stimulation of gastric, evidence reviewed for an indication is shown by small intestinal, or colonic motility and from the evidence rating. shortened transit time (Evidence rating: B-2 [table 1][table 2][table3]).{R-4-7; 17; 21-24} Cats Accepted Note: There is no evidence that cisapride is effective in ELUS,CAN EL Constipation, chronic (treatment) ; or the treatment of megaesophagus in dogs.
    [Show full text]
  • Investigating the Pharmacology of Novel 5-HT3 Receptor Ligands; with the Potential to Treat Neuropsychiatric and Gastrointestinal Disorders
    Investigating the pharmacology of novel 5-HT3 receptor ligands; with the potential to treat neuropsychiatric and gastrointestinal disorders by Alexander Roberts A thesis submitted to the University of Birmingham for the Degree of Doctor of Philosophy Institute of Clinical Sciences College of Medical and Dental Sciences University of Birmingham February 2020 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. Abstract The 5-hydroxytryptamine (5-HT; serotonin) 5-HT3 receptor is an excitatory ligand- gated ion channel expressed in for example the brain and the gastrointestinal tract. Two major subtypes of the receptor have been studied in the most detail; the homomeric 5-HT3A receptor and the heteromeric 5-HT3AB receptor. 5-HT3 receptor antagonists are used clinically to treat chemotherapy induced and post-operative nausea and vomiting, and demonstrate symptomatic relief in diarrhoea-predominant irritable bowel syndrome (IBS-d); but unfortunately, these medications cause adverse effects such as constipation or rarely ischemic colitis in the latter condition. This study has characterised the pharmacology of two structurally distinct 5-HT3 receptor partial agonists (vortioxetine and CSTI-300); and identified the unique binding properties of the cryptic orthosteric modulator 5-chloroindole (Cl-indole) for the human (h) 5-HT3 receptor.
    [Show full text]
  • A Phase 2B, Randomized, Multicenter, Double
    Title: A Phase 2b, Randomized, Multicenter, Double-Blind, Dose-Ranging Study to Assess the Efficacy, Safety and Pharmacokinetics of Intravenous TAK-954 in Critically Ill Patients With Enteral Feeding Intolerance NCT Number: NCT03477903 Protocol Approve Date: 28 February 2018 Certain information within this protocol has been redacted (ie, specific content is masked irreversibly from view with a black/blue bar) to protect either personally identifiable information (PPD) or company confidential information (CCI). This may include, but is not limited to, redaction of the following: Named persons or organizations associated with the study. Proprietary information, such as scales or coding systems, which are considered confidential information under prior agreements with license holder. • Other information as needed to protect confidentiality of Takeda or partners, personal information, or to otherwise protect the integrity of the clinical study. TAKEDA PHARMACEUTICALS PROTOCOL A Phase 2b, Randomized, Multicenter, Double-Blind, Dose-Ranging Study to Assess the Efficacy, Safety and Pharmacokinetics of Intravenous TAK-954 in Critically Ill Patients With Enteral Feeding Intolerance TAK-954 in Critically Ill Patients With Enteral Feeding Intolerance Sponsor: Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited Please note: Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, may be referred to in this protocol as “Millennium,” “Sponsor,” or “Takeda”. Study Number: 2002 IND Number: 114408 EudraCT Number: 2017-003206-41 Compound: TAK-954 Date: 28 February 2018 Version/Amendment 01 Number: Amendment History: Amendment Type (for regional Date Amendment Number Europe purposes only) Region 16 Jan 2018 Initial version Not applicable Global* 28 February 2018 01 Nonsubstantial Global* CONFIDENTIAL PROPERTY OF TAKEDA This document is a confidential communication of Takeda.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2016/0051466A1 FARR Et Al
    US 2016.005 1466A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0051466A1 FARR et al. (43) Pub. Date: Feb. 25, 2016 (54) NOVEL FORMULATIONS FORTREATMENT Publication Classification OF MIGRAINE (51) Int. Cl. 71) Applipplicant: ZOGENIX,9 INC.... E.EmeryV1lle, ille, CA (US A619/00 2006.O1 A613 L/478 (2006.01) (72) Inventors: Stephen J. FARR, Orinda, CA (US); A613 L/4045 (2006.01) John TURANIN, Danville, CA (US); (52) U.S. Cl. Roger HAWLEY, Rancho Santa Fe, CA CPC ........... A61 K9/0019 (2013.01); A61 K3I/4045 SS Jeffrey A. Schuster, Bolinas, CA (2013.01); A61 K31/4178 (2013.01) (57) ABSTRACT (21) Appl. No.: 14/930,982 Systems and methods are described for treating un-met medi (22) Filed: Nov. 3, 2015 cal needs in migraine and related conditions such as cluster headache. Included are treatments that are both rapid onset Related U.S. Application Data and long acting, which include Sustained release formula tions, and combination products. Also included are treat (60) Continuationonunuation oIof application No. 13/863,686,oso, filedIlled on ments ford multiplecombination symptoms products. of migraine, Also included especially head Apr.of 16, 2013, which is a division220 of application No. acheh andd nausea andd Vomiting. Systems thath are se1f filed as -application - - - No. PCT/US2009/002533• 1s s on Apr.s contained, portable, prefilled, and simple to self administer at 24, 2009 the onset of a migraine attack a disclosed, and preferably s include a needle-free injector and a high Viscosity formula (60) Provisional application No. 61/048.463, filed on Apr.
    [Show full text]
  • Surveillance Review Proposal PDF 387 KB
    National Institute for Health and Care Excellence Surveillance programme Surveillance proposal consultation document Irritable bowel syndrome NICE guideline CG61 – 8-year surveillance review Background information Guideline issue date: February 2008 3-year review (no update)* 6-year review (yes to update) *Although the 3-year review decision was no update, the findings were subsequently used to pilot the NICE’s rapid update process. Surveillance proposal for consultation We will not update the guideline at this time. Reason for the proposal New evidence We found 105 new studies in a search for randomised controlled trials (RCTs) and systematic reviews published between 01 September 2013 and 18 July 2016. We also considered studies identified by members of the guideline committee who originally worked on this guideline. Evidence identified in previous surveillance 3 years and 6 years after publication of the guideline was also considered. This included 52 studies identified by search. From all sources, 157 studies were considered to be relevant to the guideline. Surveillance proposal consultation document for Irritable bowel syndrome (2008) NICE guideline CG61 1 of 44 This included new evidence that is consistent with current recommendations on: diagnosis of irritable bowel syndrome (IBS) dietary interventions physical activity interventions drug treatments (antispasmodics, laxatives, anti-motility agents and antidepressants) psychotherapy hypnotherapy, biofeedback and relaxation therapy acupuncture and patient information. We also identified new evidence in the following areas that was inconsistent with, or not covered by, current recommendations, but the evidence was not considered to impact on the guideline: ondansetron vitamin D supplementation herbal medicines. We did not find any new evidence on reflexology, psychosocial interventions, or self-help and support groups.
    [Show full text]