DOCSLIB.ORG

Serotonin 5-Ht3 Receptor Antagonists for Use in The

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Serotonin 5-Ht3 Receptor Antagonists for Use in The (19) TZZ ¥ _T (11) EP 2 432 467 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 31/4178 (2006.01) A61K 31/4184 (2006.01) 21.02.2018 Bulletin 2018/08 A61K 31/437 (2006.01) A61K 31/439 (2006.01) A61K 31/46 (2006.01) A61K 31/4747 (2006.01) (2006.01) (2006.01) (21) Application number: 10723060.9 A61K 31/496 A61K 31/538 A61P 1/08 (2006.01) A61P 43/00 (2006.01) (22) Date of filing: 20.05.2010 (86) International application number: PCT/EP2010/056953 (87) International publication number: WO 2010/133663 (25.11.2010 Gazette 2010/47) (54) SEROTONIN 5-HT3 RECEPTOR ANTAGONISTS FOR USE IN THE TREATMENT OF LESIONAL VESTIBULAR DISORDERS SEROTONIN-5-HT3-REZEPTOR-ANTAGONISTEN ZUR VERWENDUNG BEI DER BEHANDLUNG VON VESTIBULÄREN LÄSIONSSTÖRUNGEN ANTAGONISTES DU RÉCEPTEUR 5-HT3 DE LA SÉROTONINE POUR LEUR UTILISATION DANS LE TRAITEMENT D’UN TROUBLE LÉSIONNEL VESTIBULAIRE (84) Designated Contracting States: • BROOKES G B: "The pharmacological treatment AL AT BE BG CH CY CZ DE DK EE ES FI FR GB of Menière’s disease." CLINICAL GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO OTOLARYNGOLOGY AND ALLIED SCIENCES PL PT RO SE SI SK SM TR FEB 1996 LNKD- PUBMED:8674219, vol. 21, no. 1, February 1996 (1996-02), pages 3-11, (30) Priority: 20.05.2009 EP 09305464 XP002591311 ISSN: 0307-7772 21.10.2009 EP 09305996 • MANDELCORNJEFF ET AL:"A preliminary study of the efficacy of ondansetron in the treatment of (43) Date of publication of application: ataxia, poor balance and incoordination from 28.03.2012 Bulletin 2012/13 brain injury." BRAIN INJURY : [BI] OCT 2004, vol. 18, no. 10, October 2004 (2004-10), pages (73) Proprietor: INSERM (Institut National de la Santé 1025-1039, XP008109968 ISSN: 0269-9052 et de la Recherche Médicale) • KRAUT L ET AL: "ANTI-EMETICS FOR CANCER 75013 Paris (FR) CHEMOTHERAPY-INDUCED EMESIS: POTENTIAL OF ALTERNATIVE DELIVERY (72) Inventors: SYSTEMS" DRUGS, ADIS INTERNATIONAL LTD, • CHABBERT, Christian NZ LNKD- F-34295 MONTPELLIER Cedex 05 (FR) DOI:10.2165/00003495-200161110-00003, vol. 61, • VENAIL, Frédéric no. 11, 1 January 2001 (2001-01-01), pages F-34295 MONTPELLIER Cedex 05 (FR) 1553-1562, XP009047329 ISSN: 0012-6667 • MUCHATUTA N A ET AL: "Management of (74) Representative: Icosa postoperative nausea and vomiting : focus on 83 avenue Denfert-Rochereau palonosetron", THERAPEUTICS AND CLINICAL 75014 Paris (FR) RISKMANAGE, DOVE MEDICAL PRESS LTD., NZ, vol. 5, 1 January 2007 (2007-01-01), pages 21-34, (56) References cited: XP008114229, ISSN: 1176-6336 EP-A2- 1 250 925 US-A- 4 695 578 US-A- 5 360 800 US-A- 6 063 802 Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 2 432 467 B1 Printed by Jouve, 75001 PARIS (FR) (Cont. next page) EP 2 432 467 B1 Remarks: Thefile contains technical information submitted after the application was filed and not included in this specification 2 EP 2 432 467 B1 Description FIELD OF THE INVENTION 5 [0001] The invention relates to serotonin 5-HT3 receptor antagonists selected from the group consisting of azasetron, tropisetron, palonosetron, lerisetron, alosetron, granisetron, dolasetron, bemesetron, ramosetron, itasetron, zacopride and cilansetron, for use in the treatment or prevention of a lesional vestibular disorder. BACKGROUND OF THE INVENTION 10 Introduction on vestibular disorders [0002] Vestibular (inner ear) disorders can cause dizziness, vertigo, imbalance, hearing changes, nausea, fatigue, anxiety, difficulty concentrating, and other symptoms, with potentially devastating effects on a person’s day-to-day 15 functioning, ability to work, relationships with family and friends, and quality of life. [0003] For example, vestibular neuritis is the first cause of hospitalisation for non-neurological vertigos. Because its aetiology is largely unknown, epidemiological studies are variable depending on the source (its incidence is believed to be between 3.5 and 50 new cases for 100000 persons/per year). In the past, either an inflammation of the vestibular nerve or labyrinthine ischemia was proposed as a cause of vestibular neuritis. Currently, a viral cause is favoured. A 20 reactivation of herpes simplex virus type 1 would explain the repetition of the vertigo crisis under such a situation. [0004] Vestibular disorders may also be involved in the majority of the fall in the elderly and their prevention became a priority. The fall in the elderly represents indeed more than 1% of the total budget of the health insurance in France (INSEE 1990). It affects in France 30% of people above 65 and 50% above 80. The fall in the elderly is involved in 2/3 of the death caused by accident above 65, and multiplies by 4 the risk of death in the following year. 25 Aetiology of vestibular disorders [0005] Although the aetiology of vestibular disorders is mostly unknown, it is widely accepted that vestibular disorders (also called vestibular deficits) constitute a vast family of conditions wherein the vestibule organ is associated. These 30 disorders may be distinguished by their putative origins. One can thus identify (1) lesional vestibular disorders and (2) non lesional vestibular disorders. 1) Lesional vestibular disorders refer to vestibular disorders wherein lesions on inner ear cells and/or vestibular nerve are present or will appear during the disorder time course. In this case, the functionality of the vestibule is 35 impaired as it can be observed using clinical functional tests (VOR, VNG). Lesional vestibular disorders include: - vestibular disorders wherein an infection inflames the inner ear and/or the vestibular nerve inducing reversible and/or irreversible damages. One example of conditions from this group is vestibular neuritis. - vestibular disorders wherein inner ear fluid levels are affected (abnormalities in the quantity, composition, and/or 40 pressure of the endolymph). These disorders usually develop lesions during the disease time course. Examples of conditions from this group are Ménière’s disease and secondary endolymphatic hydrops. They are currently associated with tinnitus and hearing loss. - Vestibular disorders induced by insults or lesions of the vestibular endorgans. Examples of said conditions are vertigo caused by local ischemia, excitotoxicity, and trauma that affect temporal bones. 45 2) Non-lesional vestibular disorders refer to vestibular disorders supported by transient and often iterative vertigo crisis wherein no lesion on inner ear cells and/or vestibular nerve can be observed. In this case, the functionality of the vestibule evaluated between the vertigo crisis using functional tests (VOR, VNG) does not differ from healthy vestibule. Non-lesional vestibular disorders include: 50 - vestibular disorders wherein debris had been collected within a part of the inner ear. This debris, called otoconia, is made up of small crystals of calcium carbonate which send false signals to the brain when they shift. Examples of said conditions are positional vertigos. - Iterative vestibular disorders of unknown origin without tinnitus or hearing loss. 55 Evaluation of the vestibule functional loss [0006] In human, morphofunctional alterations of the vestibular endorgans cannot be evaluated directly (excepted for 3 EP 2 432 467 B1 large lesions that can be detected by IRM). Rather indirect assessment methods are currently used to evaluate the loss of functionality of the vestibule. These behaviour testing methods are generally conducted at ENT clinic/hospitals. Among them, we can cite the vestibulonystagmography (VNG), and assessment of the vestibuloocculomotor reflex (VOR) using caloric or rotational tests. 5 Treatments of vestibular deficits [0007] Current treatments of vestibular deficits mainly focus on reducing the vertigo crisis using vestibuloplegic drugs, while limiting neurovegetative reactions by using anti-emetic drugs. Corticosteroids and antiviral drugs are the only 10 medications that try to limit the spread of vestibular damages in the case of vestibular neuritis (that are assumed to be due to bacterial or virus infections). Their effect remains under debate regarding the lack of aetiology in most vestibular deficits. For example, recovery after vestibular neuritis is usually incomplete. In a study of 60 patients, horizontal sem- icircular canal paresis was found in about 90% one month after the onset of symptoms, and in 80% after six months; the caloric responses normalized in only 42%. On the basis of the incidence of this condition, a substantial and permanent 15 unilateral dynamic deficit of the vestibulo-ocular reflex, which cannot be compensated for by other mechanisms, develops in approximately 4000 persons per year in the United States. This deficit leads to impaired vision and postural imbalance during walking, and especially during head movement toward the affected ear. [0008] Accordingly, there is a need for a protective or repair therapy that prevents, reduces or treats the incidence and/or severity of lesional vestibular disorders, said functional alteration of the inner ear cells and/or vestibular nerve 20 being due to an inflammation, lesions or insults of diverse origins. [0009] The Inventors surprisingly found that serotonin 5-HT3 receptors antagonists, such as ondansetron, were able to prevent or treat vestibular lesions by protecting inner ear cells and vestibular nerve from damage or degeneration. Ondansetron is known from Jellish et al. (Journal of Clinical Anesthesia 2007, 9:451-456) for reduction of postoperative nausea or vomiting after chirurgical treatment of the middle ear. In particular, ondansetron was known for preventing 25 severe vomiting after destructive surgery (such as vestibular nerve section or labyrinthectomy) in Ménière’s disease patients (Brookes GB, Clin Otolaryngol Allied Sci.
Load more

Recommended publications
  • Focusing on the Re-Emergence of Primitive Reflexes Following Acquired Brain Injuries
    33 Focusing on The Re-Emergence of Primitive Reflexes Following Acquired Brain Injuries Resiliency Through Reconnections - Reflex Integration Following Brain Injury Alex Andrich, OD, FCOVD Scottsdale, Arizona Patti Andrich, MA, OTR/L, COVT, CINPP September 19, 2019 Alex Andrich, OD, FCOVD Patti Andrich, MA, OTR/L, COVT, CINPP © 2019 Sensory Focus No Pictures or Videos of Patients The contents of this presentation are the property of Sensory Focus / The VISION Development Team and may not be reproduced or shared in any format without express written permission. Disclosure: BINOVI The patients shown today have given us permission to use their pictures and videos for educational purposes only. They would not want their images/videos distributed or shared. We are not receiving any financial compensation for mentioning any other device, equipment, or services that are mentioned during this presentation. Objectives – Advanced Course Objectives Detail what primitive reflexes (PR) are Learn how to effectively screen for the presence of PRs Why they re-emerge following a brain injury Learn how to reintegrate these reflexes to improve patient How they affect sensory-motor integration outcomes How integration techniques can be used in the treatment Current research regarding PR integration and brain of brain injuries injuries will be highlighted Cases will be presented Pioneers to Present Day Leaders Getting Back to Life After Brain Injury (BI) Descartes (1596-1650) What is Vision? Neuro-Optometric Testing Vision writes spatial equations
    [Show full text]
  • )&F1y3x PHARMACEUTICAL APPENDIX to THE
    )&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE
    [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]
  • 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]
  • 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]
  • α2-Adrenoceptor and 5-Ht3 Serotonin Receptor
    Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2012 α2-ADRENOCEPTOR AND 5-HT3 SEROTONIN RECEPTOR LIGANDS AS POTENTIAL ANALGESIC ADJUVANTS Genevieve Alley Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Pharmacy and Pharmaceutical Sciences Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/2867 This Dissertation is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. © Genevieve Sirles Alley 2012 All Rights Reserved i α2-ADRENOCEPTOR AND 5-HT3 SEROTONIN RECEPTOR LIGANDS AS POTENTIAL ANALGESIC ADJUVANTS A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. by Genevieve Sirles Alley Bachelor of Science in Biology, Virginia Commonwealth University 2005 Director: Małgorzata Dukat, Ph.D. Associate Professor, Department of Medicinal Chemistry Virginia Commonwealth University Richmond, Virginia August 2012 ii ACKNOWLEDGMENT First, I would like to thank Dr. Małgorzata Dukat for her continued assistance and advice throughout my studies. This guidance has helped me better understand and appreciate medicinal chemistry. Also, a special thanks is given to both Dr. Dukat and Dr. Richard A. Glennon for their constant quizzing during group meetings, which not only helped me recongnize what I did not already understand, but also, improved my ability to devise potential solutions for future research problems. Furthermore, I could not have successfully completed this dissertation work without the help of Dr.
    [Show full text]
  • Analyzing in Vitro Results for the 5-HT Ligands
    APPLICATION NOTE Analyzing In Vitro Results for the 5-HT Ligands REACHING A DEEPER UNDERSTANDING OF LIGAND–RECEPTOR INTERACTIONS Effective drug discovery depends on a deep understanding of the function and therapeutic potential of a compound as well as a clear picture of the chemical structure and druggability of the compound. Using the example of serotonin receptors, this application note looks at how in vitro data from Reaxys® Medicinal Chemistry facilitate such studies on the interface of biology and chemistry. A systematic look at 5-HT receptor family ligands could reveal even broader possibilities for their therapeutic application. The study of serotonin (5-HT) receptor pharmacology has been and remains an area of major interest for pharmaceutical research. Indeed, in the last 50 years, drugs directly or indirectly targeting these receptors have emerged as important therapeutic agents, providing treatments for a broad range of clinical conditions. Many different serotonin receptor subtypes have been described in the literature 1,( 2). The 5-HT1, 5-HT2, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 receptor families all belong to the G-protein- coupled receptor (GPCR) class A superfamily (3). The 5-HT1 receptor family is one of the most complex in terms of molecular diversity and pharmacological interactions. Selective 5-HT1B/1D receptor agonists, such as sumatriptan and rizatriptan, have established a new standard in the acute treatment of migraine headaches. Unlike other serotonin receptors, the 5-HT3 receptor is not a GPCR but a ligand-gated ion channel. Its ligands have been extensively studied. Selective antagonists at 5-HT3 receptors have transformed cancer therapy by preventing chemotherapy- and radiation-induced emesis.
    [Show full text]
  • Novel Analogs of M-Chlorophenylguanidine As 5-HT3 Receptor Ligands Katie Alix Virginia Commonwealth University
    Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2009 Novel Analogs of m-Chlorophenylguanidine as 5-HT3 Receptor Ligands Katie Alix Virginia Commonwealth University Follow this and additional works at: http://scholarscompass.vcu.edu/etd Part of the Chemicals and Drugs Commons © The Author Downloaded from http://scholarscompass.vcu.edu/etd/1734 This Thesis is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. © Katie Elizabeth Alix 2008 All Rights Reserved NOVEL ANALOGS OF m-CHLOROPHENYLGUANIDINE AS 5-HT3 RECEPTOR LIGANDS A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University. by KATIE ELIZABETH ALIX Bachelor of Science in Biochemistry, Virginia Tech 2006 Bachelor of Arts in Chemistry, Virginia Tech 2006 Director:MAŁGORZATA DUKAT Associate Professor, Department of Medicinal Chemistry Virginia Commonwealth University Richmond, Virginia May 2009 Acknowledgement First, I would like to thank Dr. Dukat for her patience and guidance over the last three years. She has helped mold me into a better scientist with a deeper understanding and appreciation of medicinal chemistry as an entire discipline. I would like to thank Dr. Richard Glennon for his help with my thesis and numerous useful insights. I would also like to thank Dr. Richard Young, Jessica Worsham, and Genevieve Sirles for teaching me how to handle mice and the various animal assays. I would also like to thank Dr.
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,158,152 B2 Palepu (45) Date of Patent: Apr
    US008158152B2 (12) United States Patent (10) Patent No.: US 8,158,152 B2 Palepu (45) Date of Patent: Apr. 17, 2012 (54) LYOPHILIZATION PROCESS AND 6,884,422 B1 4/2005 Liu et al. PRODUCTS OBTANED THEREBY 6,900, 184 B2 5/2005 Cohen et al. 2002fOO 10357 A1 1/2002 Stogniew etal. 2002/009 1270 A1 7, 2002 Wu et al. (75) Inventor: Nageswara R. Palepu. Mill Creek, WA 2002/0143038 A1 10/2002 Bandyopadhyay et al. (US) 2002fO155097 A1 10, 2002 Te 2003, OO68416 A1 4/2003 Burgess et al. 2003/0077321 A1 4/2003 Kiel et al. (73) Assignee: SciDose LLC, Amherst, MA (US) 2003, OO82236 A1 5/2003 Mathiowitz et al. 2003/0096378 A1 5/2003 Qiu et al. (*) Notice: Subject to any disclaimer, the term of this 2003/OO96797 A1 5/2003 Stogniew et al. patent is extended or adjusted under 35 2003.01.1331.6 A1 6/2003 Kaisheva et al. U.S.C. 154(b) by 1560 days. 2003. O191157 A1 10, 2003 Doen 2003/0202978 A1 10, 2003 Maa et al. 2003/0211042 A1 11/2003 Evans (21) Appl. No.: 11/282,507 2003/0229027 A1 12/2003 Eissens et al. 2004.0005351 A1 1/2004 Kwon (22) Filed: Nov. 18, 2005 2004/0042971 A1 3/2004 Truong-Le et al. 2004/0042972 A1 3/2004 Truong-Le et al. (65) Prior Publication Data 2004.0043042 A1 3/2004 Johnson et al. 2004/OO57927 A1 3/2004 Warne et al. US 2007/O116729 A1 May 24, 2007 2004, OO63792 A1 4/2004 Khera et al.
    [Show full text]
  • Static Reflexes
    Te xt . Important Lecture . Formulas No.16 . Numbers . Doctor notes “Believe In Your Dreams. They . Notes and explanation Were Given To You For A Reason” 1 Physiology of postural reflexes Objectives: 1. Postural reflexes are needed to keep the body in a proper position while standing, moving. When body posture is suddenly altered it is corrected by Sevier reflexes. These reflexes are operating at spinal cord, medulla, mid-brain and cortical levels. To make the reflex movements smooth cerebellum, basal ganglia and vestibular apparatus are needed. Students are required to know posture-regulating parts of CNS. 2 What is posture? ONLY IN MALES’ SLIDES ONLY IN FEMALES’ SLIDES Posture is the attitude taken by the body in any It is maintenance of upright position against gravity particular situation like standing posture, sitting (center of body is needed to be between the legs) it needs posture, etc.. Even during movement, there is a continuously changing posture. anti-garvity muscles (Extensor muscles). Up-right posture need postural reflexes. The basis of posture is the ability to keep certain Posture depends on muscle tone (stretch reflex) ( basic group of muscles in sustained contraction for long periods. Variation in the degree of contraction and postural reflex). tone in different groups of muscle decides the The main pathways concerned with posture are: posture of the individual. Medial tracts: control proximal limbs & axial muscles for posture & gross movements. Lateral pathways: as corticospinal-rubrospinal control distal limbs. 3 ONLY IN MALES’ SLIDES Postural reflex These reflexes resist displacement of the body caused by gravity or acceleratory forces, and they have the following functions: 1.
    [Show full text]
  • WO 2007/061529 Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date (10) International Publication Number 31 May 2007 (31.05.2007) PCT WO 2007/061529 Al (51) International Patent Classification: GB, GD, GE, GH, GM, HN, HR, HU, ID, IL, IN, IS, JP, A61K 9/14 (2006.01) KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LV,LY,MA, MD, MG, MK, MN, MW, MX, MY, MZ, (21) International Application Number: NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, PCT/US2006/040197 SC, SD, SE, SG, SK, SL, SM, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW (22) International Filing Date: 13 October 2006 (13.10.2006) (84) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of regional protection available): ARIPO (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (26) Publication Language: English ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European (AT,BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HU, IE, IS, IT, LT, LU, LV,MC, NL, PL, PT, (30) Priority Data: RO, SE, SI, SK, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, 11/282,507 18 November 2005 (18.1 1.2005) US GN, GQ, GW, ML, MR, NE, SN, TD, TG). (71) Applicant (for all designated States except US): SCI- Declarations under Rule 4.17: DOSE PHARMA INC.
    [Show full text]