DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2017/0071522 A1 PARSEY Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) Patent Application Publication (10) Pub. No.: US 2017/0071522 A1 PARSEY Et Al US 2017007 1522A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2017/0071522 A1 PARSEY et al. (43) Pub. Date: Mar. 16, 2017 (54) METHOD OF DAGNOSING DEPRESSION A6B 5/55 (2006.01) BY PET IMAGING A6IB5/00 (2006.01) A6IB 6/03 (2006.01) (71) Applicants: Ramin PARSEY, East Setauket, NY A6IB 6/00 (2006.01) (US); Christine DELORENZO, Long (52) U.S. Cl. Island City, NY (US); Gregory CPC .............. A61 B 5/165 (2013.01); A61B 6/037 SULLIVAN, New York, NY (US) (2013.01); A61B 6/481 (2013.01); A61 B 5/055 (2013.01); A61 B 5/0042 (2013.01); A61B (72) Inventors: Ramin PARSEY, East Setauket, NY 6/501 (2013.01); A61B 6/5217 (2013.01); (US); Christine DELORENZO, Long Island City, NY (US); Gregory A61 K5I/0459 (2013.01) SULLIVAN, New York, NY (US) (57) ABSTRACT (73) Assignees: THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, Albany, NY (US): THE The present invention provides a method of determining TRUSTEES OF COLUMBIA whether a subject is afflicted with a depressive disorder UNIVERSITY IN THE CITY OF comprising: NEW YORK, New York, NY (US) (i) introducing into the Subject a positron emission tomog raphy (PET) radioligand capable of binding with a (21) Appl. No.: 15/121,957 serotonin 5-HT, receptor, (22) PCT Fed: Mar. 5, 2015 (ii) performing one or more PET scans of the subject; (iii) determining, by analysis of the one or more PET (86) PCT No.: PCT/US2O15/O18992 images, a receptor binding potential of the PET radio S 371 (c)(1), ligand for the serotonin 5-HT, receptor in a region of (2) Date: Aug. 26, 2016 interest in the subject; (iv) comparing the receptor binding potential value of the Related U.S. Application Data PET radioligand in the region of interest in the subject (60) Provisional application No. 61/949,743, filed on Mar. to a predetermined receptor binding potential threshold 7, 2014. value; and (V) classifying the Subject as having the depressive dis Publication Classification order or as not having the depressive disorder based on (51) Int. C. the comparison of step (iv), thereby determining A6 IB 5/16 (2006.01) whether the subject is afflicted with the depressive A6 IK 5L/04 (2006.01) disorder. Patent Application Publication Mar. 16, 2017. Sheet 1 of 2 US 2017/0071522 A1 Fig. Raphe 8PF in Raies 120; : Sensitivity: 87.5% 100: Specificity: 96% Controis (ne2s) tres Patent Application Publication Mar. 16, 2017. Sheet 2 of 2 US 2017/0071522 A1 140 Raphe 8PF in iaiss 120 4. o US 2017/007 1522 A1 Mar. 16, 2017 METHOD OF DAGNOSING DEPRESSION Tomography (PET) allow visualization and quantification of BY PET IMAGING serotonin receptor binding in vivo. 0007 PET involves detection of pairs of gamma rays 0001. This application claims priority of U.S. Provisional emitted indirectly by a positron-emitting radionuclide Application No. 61/949,743, filed Mar. 7, 2014, the contents (tracer) injected into the body. Images of tracer concentra of which are hereby incorporated by reference. tion in the body are then reconstructed by computer analysis. 0002 Throughout this application, certain publications Positron emitting isotopes include carbon, iodine, fluorine, are referenced in parentheses. Full citations for these pub nitrogen, and oxygen. These isotopes can replace their lications may be found immediately preceding the claims. non-radioactive counterparts in target compounds to pro The disclosures of these publications in their entireties are duce tracers that function biologically and are chemically hereby incorporated by reference into this application in identical to the original molecules for PET imaging, or can order to describe more fully the state of the art to which this be attached to said counterparts to give close analogues of invention relates. the respective parent molecule. Among these isotopes, F is 0003. The invention was made with government support a convenient labeling isotope due to its relatively long under Grant numbers MH40695, MH62185, 1MH074813, 109-minute half-life. and MHO90276 awarded by the National Institutes of Health. The government has certain rights in the invention. SUMMARY OF THE INVENTION BACKGROUND OF THE INVENTION 0008. The present invention provides a method of deter mining whether a subject is afflicted with a depressive 0004 Major depressive disorder (MDD) is a highly disorder comprising: prevalent psychiatric diagnosis that is associated with a high 0009 (i) introducing into the subject a positron emis degree of morbidity and mortality (Marangell et al., 2006; sion tomography (PET) radioligand capable of binding Merikangas et al., 2007; Woods, 2000). This debilitating with a serotonin 5-HT, receptor; disorder is currently one of the leading causes of disability 0.010 (ii) performing one or more PET scans of the nationwide among both medical and psychiatric conditions Subject; and is predicted to be the leading cause of disease burden by 0.011 (iii) determining, by analysis of the one or more the year 2030 (Lopez & Murray, 1998: World Health, 2004). PET images, a receptor binding potential of the PET 0005. There are currently 945 ways to meet diagnostic radioligand for the serotonin 5-HT" A receptor in a criteria for a major depressive episode and thus, patients region of interest in the subject; sharing as few as one common symptom can be diagnosed 0012 (iv) comparing the receptor binding potential with major depression. Further, diagnosis of MDD depends value of the PET radioligand in the region of interest in on the reliability of current diagnostic classifications and the Subject to a predetermined receptor binding poten (Subjective) structured diagnostic interviews (Karlsson et tial threshold value; and al., 2010). It is partly for this reason that, for several decades, 0013 (V) classifying the subject as having the depres epidemiological studies reported that women were twice as sive disorder or as not having the depressive disorder likely as men to develop MDD, with prevalence rates of 8% based on the comparison of step (iv), thereby deter and 4%, respectively (Jovanovic et al., 2008: Parker & mining whether the subject is afflicted with the depres Brotchie, 2010). Since men and women experience depres sive disorder. sion differently, these subjective criteria may have led to an 0014. The present invention also provides a method of under diagnosis of MDD in males. Consistent with this view, preparing a report classifying a subject as having a depres a 2013 study reported that when changes in case definitions sive disorder or as not having a depressive disorder which of MDD were implemented in a way that account for higher comprises: rates of anger, aggression and Substance abuse in men, MDD 0.015 (i) receiving the data of one or more PET scans prevalence estimates between sexes are eliminated (Martin of the subject performed by a PET imaging device after et al., 2013). a PET radioligand for a serotonin 5-HT, receptor was 0006. A biomarker is a characteristic that can be objec introduced into the subject; tively measured and used as an indicator of either normal or 0016 (ii) processing the data to determine a receptor pathogenic processes (Singh & Rose, 2009). Identification binding potential of the PET radioligand for the sero of psychiatric biomarkers for MDD would eliminate the tonin 5-HT, receptor in a region of interest in the need for Subjective diagnosis, and therefore help improve Subject and comparing the receptor binding potential diagnostic classification. Further, Such a marker may aid in better classifying the great heterogeneity observed across value to a predetermined receptor binding potential MDD presentation into more specific Sub-diagnostic catego threshold value; and ries as well as provide much needed evidence of the physi 0017 (iii) populating a report classifying the subject. ological underpinnings of MDD (Singh & Rose, 2009). Due 0018. The present invention further provides a method of to its role in MDD, the serotonergic system could give rise treating a subject afflicted with a depressive disorder, com to a biomarker of depression. Previous research has impli prising cated the serotonergic system in MDD pathophysiology 0.019 (a) determining whether the subject is afflicted (Boldrini et al., 2008: Drevets et al., 1999; Parsey et al., with the depressive disorder comprising: 2006; Sargent et al., 2000: Savitz et al., 2009; Stockmeier, 0020 (i) introducing into the subject a positron 2003) and Selective Serotonin Reuptake Inhibitors (SSRIs) emission tomography (PET) radioligand capable of remain the first line MDD treatment, further implicating binding with a serotonin 5-HT, receptor, serotonergic dysfunction in MDD (Blier et al. 1998; G. M. 0021 (ii) performing one or more PET scans of the Sullivan et al., 2009). Tools such as Positron Emission Subject; US 2017/007 1522 A1 Mar. 16, 2017 0022 (iii) determining, by analysis of the one or 0030 (ii) performing one or more PET scans of the more PET images, a receptor binding potential of the Subject; PET radioligand for the serotonin 5-HT, receptor in 0.031 (iii) determining, by analysis of the one or more a region of interest in the Subject; PET images, a receptor binding potential of the PET 0023 (iv) comparing the receptor binding potential radioligand for the serotonin 5-HT, receptor in a value of the radioligand in the region of interest in region of interest in the Subject; the Subject to a predetermined receptor binding 0.032 (iv) comparing the receptor binding potential potential threshold value; and value of the PET radioligand in the region of interest in 0024 (V) classifying the subject as afflicted with the the Subject to a predetermined receptor binding poten depressive disorder when the receptor binding poten tial threshold value; and tial value of the radioligand in the Subject is greater 0033 (V) classifying the subject as having the depres than the predetermined diagnostic threshold value; sive disorder or as not having the depressive disorder and based on the comparison of step (iv), thereby deter mining whether the subject is afflicted with the depres 0025 (b) treating the subject based on the determina sive disorder.
Load more

Recommended publications
  • Modifications to the Harmonized Tariff Schedule of the United States To
    U.S. International Trade Commission COMMISSIONERS Shara L. Aranoff, Chairman Daniel R. Pearson, Vice Chairman Deanna Tanner Okun Charlotte R. Lane Irving A. Williamson Dean A. Pinkert Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436 U.S. International Trade Commission Washington, DC 20436 www.usitc.gov Modifications to the Harmonized Tariff Schedule of the United States to Implement the Dominican Republic- Central America-United States Free Trade Agreement With Respect to Costa Rica Publication 4038 December 2008 (This page is intentionally blank) Pursuant to the letter of request from the United States Trade Representative of December 18, 2008, set forth in the Appendix hereto, and pursuant to section 1207(a) of the Omnibus Trade and Competitiveness Act, the Commission is publishing the following modifications to the Harmonized Tariff Schedule of the United States (HTS) to implement the Dominican Republic- Central America-United States Free Trade Agreement, as approved in the Dominican Republic-Central America- United States Free Trade Agreement Implementation Act, with respect to Costa Rica. (This page is intentionally blank) Annex I Effective with respect to goods that are entered, or withdrawn from warehouse for consumption, on or after January 1, 2009, the Harmonized Tariff Schedule of the United States (HTS) is modified as provided herein, with bracketed matter included to assist in the understanding of proclaimed modifications. The following supersedes matter now in the HTS. (1). General note 4 is modified as follows: (a). by deleting from subdivision (a) the following country from the enumeration of independent beneficiary developing countries: Costa Rica (b).
    [Show full text]
  • I Regulations
    23.2.2007 EN Official Journal of the European Union L 56/1 I (Acts adopted under the EC Treaty/Euratom Treaty whose publication is obligatory) REGULATIONS COUNCIL REGULATION (EC) No 129/2007 of 12 February 2007 providing for duty-free treatment for specified pharmaceutical active ingredients bearing an ‘international non-proprietary name’ (INN) from the World Health Organisation and specified products used for the manufacture of finished pharmaceuticals and amending Annex I to Regulation (EEC) No 2658/87 THE COUNCIL OF THE EUROPEAN UNION, (4) In the course of three such reviews it was concluded that a certain number of additional INNs and intermediates used for production and manufacture of finished pharmaceu- ticals should be granted duty-free treatment, that certain of Having regard to the Treaty establishing the European Commu- these intermediates should be transferred to the list of INNs, nity, and in particular Article 133 thereof, and that the list of specified prefixes and suffixes for salts, esters or hydrates of INNs should be expanded. Having regard to the proposal from the Commission, (5) Council Regulation (EEC) No 2658/87 of 23 July 1987 on the tariff and statistical nomenclature and on the Common Customs Tariff (1) established the Combined Nomenclature Whereas: (CN) and set out the conventional duty rates of the Common Customs Tariff. (1) In the course of the Uruguay Round negotiations, the Community and a number of countries agreed that duty- (6) Regulation (EEC) No 2658/87 should therefore be amended free treatment should be granted to pharmaceutical accordingly, products falling within the Harmonised System (HS) Chapter 30 and HS headings 2936, 2937, 2939 and 2941 as well as to designated pharmaceutical active HAS ADOPTED THIS REGULATION: ingredients bearing an ‘international non-proprietary name’ (INN) from the World Health Organisation, specified salts, esters or hydrates of such INNs, and designated inter- Article 1 mediates used for the production and manufacture of finished products.
    [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]
  • Anti Leishmanial Activities of Some Antidepressant Drugs, and Antifungal Drugs
    Journal of Advance Research in Pharmacy & Biological Science ISSN: 2208-2360 Anti Leishmanial Activities of Some Antidepressant Drugs, And Antifungal Drugs. Sagar S Trivedi*, Ms Geeta.N.Lodhi, Dr.C.A .Doifode, Harsha Raut. Shri Sachhidanand shikshan Sansthan’s Taywade College of Pharmacy ,Koradi. ABSRACT Leishmanisis is wide range, worldwide, without drug, vaccine, secticide and has not sterile immunity and efforts in this field have not been successful.Leishmaniasis is a complex vector- borne disease caused by different species of Leishmania. It affects at least 12 million people worldwide. Leishmaniasis is commonly associated with poor economic conditions and immune compromised situations like HIV co infection. There is increasing in drug resistance to commonly used therapeutics as well as lack of vaccine program. This leads to a perpetual search for a new drug for leishmaniasis. This review fundamentally deals with some antidepressant drugs, and antifugal drugs showing the anti leishmanial activities. The antidepressant drugs are Imipramine, Sertraline, Ketanserin and Mianserin. Imipramine being a Tri Cyclic Antidepressant (TCA) drug kills Leishmania donovani elevating IL-12/IL-10 ratio. Sertraline belonging to the selective serotonin reuptake inhibitor (SSRI) drugs, removes parasite loads from spleen and liver probably by declining cytoplasmic ATP consumption. Ketanserin is a serotonin receptor (5- HT2A/2C) antagonist that kills both amastigotes and promastigotes probably due to inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR). Mianserin belonging to the TCA group of drug, kills both promastigote and amastigote parasites also probably due to the inhibition of HMGR. The present review will give the summarized information about putting some old antidepressant drugs for the treatment of another disease like Leishmania.
    [Show full text]
  • Antidepressants for People with Epilepsy and Depression (Review)
    Antidepressants for people with epilepsy and depression (Review) Maguire MJ, Weston J, Singh J, Marson AG This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2014, Issue 12 http://www.thecochranelibrary.com Antidepressants for people with epilepsy and depression (Review) Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . ..... 4 BACKGROUND .................................... 6 OBJECTIVES ..................................... 7 METHODS ...................................... 7 RESULTS....................................... 10 Figure1. ..................................... 11 Figure2. ..................................... 14 ADDITIONALSUMMARYOFFINDINGS . 18 DISCUSSION ..................................... 23 AUTHORS’CONCLUSIONS . 24 REFERENCES ..................................... 24 CHARACTERISTICSOFSTUDIES . 27 DATAANDANALYSES. 37 Analysis 1.1. Comparison 1 Paroxetine versus doxepin, Outcome 1 > 50% reduction in depressive symptoms. 38 Analysis 1.2. Comparison 1 Paroxetine versus doxepin, Outcome 2 Mean depression scores. 39 Analysis 1.3. Comparison 1 Paroxetine versus doxepin, Outcome 3 Withdrawals (any reason). 39 Analysis 1.4. Comparison 1 Paroxetine versus doxepin, Outcome4Adverseeffects. 40 Analysis 2.1. Comparison 2 Amitriptyline versus
    [Show full text]
  • A Abacavir Abacavirum Abakaviiri Abagovomab Abagovomabum
    A abacavir abacavirum abakaviiri abagovomab abagovomabum abagovomabi abamectin abamectinum abamektiini abametapir abametapirum abametapiiri abanoquil abanoquilum abanokiili abaperidone abaperidonum abaperidoni abarelix abarelixum abareliksi abatacept abataceptum abatasepti abciximab abciximabum absiksimabi abecarnil abecarnilum abekarniili abediterol abediterolum abediteroli abetimus abetimusum abetimuusi abexinostat abexinostatum abeksinostaatti abicipar pegol abiciparum pegolum abisipaaripegoli abiraterone abirateronum abirateroni abitesartan abitesartanum abitesartaani ablukast ablukastum ablukasti abrilumab abrilumabum abrilumabi abrineurin abrineurinum abrineuriini abunidazol abunidazolum abunidatsoli acadesine acadesinum akadesiini acamprosate acamprosatum akamprosaatti acarbose acarbosum akarboosi acebrochol acebrocholum asebrokoli aceburic acid acidum aceburicum asebuurihappo acebutolol acebutololum asebutololi acecainide acecainidum asekainidi acecarbromal acecarbromalum asekarbromaali aceclidine aceclidinum aseklidiini aceclofenac aceclofenacum aseklofenaakki acedapsone acedapsonum asedapsoni acediasulfone sodium acediasulfonum natricum asediasulfoninatrium acefluranol acefluranolum asefluranoli acefurtiamine acefurtiaminum asefurtiamiini acefylline clofibrol acefyllinum clofibrolum asefylliiniklofibroli acefylline piperazine acefyllinum piperazinum asefylliinipiperatsiini aceglatone aceglatonum aseglatoni aceglutamide aceglutamidum aseglutamidi acemannan acemannanum asemannaani acemetacin acemetacinum asemetasiini aceneuramic
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2010/0184806 A1 Barlow Et Al
    US 20100184806A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0184806 A1 Barlow et al. (43) Pub. Date: Jul. 22, 2010 (54) MODULATION OF NEUROGENESIS BY PPAR (60) Provisional application No. 60/826,206, filed on Sep. AGENTS 19, 2006. (75) Inventors: Carrolee Barlow, Del Mar, CA (US); Todd Carter, San Diego, CA Publication Classification (US); Andrew Morse, San Diego, (51) Int. Cl. CA (US); Kai Treuner, San Diego, A6II 3/4433 (2006.01) CA (US); Kym Lorrain, San A6II 3/4439 (2006.01) Diego, CA (US) A6IP 25/00 (2006.01) A6IP 25/28 (2006.01) Correspondence Address: A6IP 25/18 (2006.01) SUGHRUE MION, PLLC A6IP 25/22 (2006.01) 2100 PENNSYLVANIA AVENUE, N.W., SUITE 8OO (52) U.S. Cl. ......................................... 514/337; 514/342 WASHINGTON, DC 20037 (US) (57) ABSTRACT (73) Assignee: BrainCells, Inc., San Diego, CA (US) The instant disclosure describes methods for treating diseases and conditions of the central and peripheral nervous system (21) Appl. No.: 12/690,915 including by stimulating or increasing neurogenesis, neuro proliferation, and/or neurodifferentiation. The disclosure (22) Filed: Jan. 20, 2010 includes compositions and methods based on use of a peroxi some proliferator-activated receptor (PPAR) agent, option Related U.S. Application Data ally in combination with one or more neurogenic agents, to (63) Continuation-in-part of application No. 1 1/857,221, stimulate or increase a neurogenic response and/or to treat a filed on Sep. 18, 2007. nervous system disease or disorder. Patent Application Publication Jul. 22, 2010 Sheet 1 of 9 US 2010/O184806 A1 Figure 1: Human Neurogenesis Assay Ciprofibrate Neuronal Differentiation (TUJ1) 100 8090 Ciprofibrates 10-8.5 10-8.0 10-7.5 10-7.0 10-6.5 10-6.0 10-5.5 10-5.0 10-4.5 Conc(M) Patent Application Publication Jul.
    [Show full text]
  • Depression and Hiv Infection: Risk Factors For
    DEPRESSION AND HIV INFECTION: RISK FACTORS FOR CARDIOVASCULAR DISEASE by Jessica Renee White B.S. in Biology, Pennsylvania State University, 2006 M.S. in Bioscience Technologies, Thomas Jefferson University, 2009 Submitted to the Graduate Faculty of the Graduate School of Public Health in partial fulfillment of the requirements for the degree of Doctor of Public Health University of Pittsburgh 2015 UNIVERSITY OF PITTSBURGH GRADUATE SCHOOL OF PUBLIC HEALTH This dissertation was presented by Jessica Renee White It was defended on April 10, 2015 and approved by Matthew Freiberg, MD, MSc, Associate Professor of Medicine, School of Medicine, Vanderbilt University Joyce Bromberger, PhD, Professor of Epidemiology and Psychiatry, Graduate School of Public Health, University of Pittsburgh Chung-Chou Chang, PhD, Professor of Medicine, Biostatistics, and Clinical and Translational Science, School of Medicine and Graduate School of Public Health, University of Pittsburgh Akira Sekikawa, MD, PhD, PhD Associate Professor of Epidemiology, Graduate School of Public Health, University of Pittsburgh Dissertation Advisor: Emma Barinas-Mitchell, PhD, Assistant Professor of Epidemiology, Graduate School of Public Health, University of Pittsburgh ii Copyright © by Jessica Renee White 2015 iii DEPRESSION AND HIV INFECTION: RISK FACTORS FOR CARDIOVASCULAR DISEASE Jessica Renee White, DrPH University of Pittsburgh, 2015 ABSTRACT Depression, a common mental health disorder, is associated with higher risk of cardiovascular disease (CVD). Adults with HIV infection
    [Show full text]
  • Genotoxic Impurities in Pharmaceutical Manufacturing: Sources, Regulations, and Mitigation † ‡ § ‡ Gyorgy Szekely,*, Miriam C
    Review pubs.acs.org/CR Genotoxic Impurities in Pharmaceutical Manufacturing: Sources, Regulations, and Mitigation † ‡ § ‡ Gyorgy Szekely,*, Miriam C. Amores de Sousa, Marco Gil, Frederico Castelo Ferreira,*, § and William Heggie*, † School of Chemical Engineering & Analytical Science, The University of Manchester, The Mill, Sackville Street, Manchester M13 9PL, United Kingdom ‡ Department of Bioengineering and Institute for Bioengineering and Biosciences (iBB), Instituto Superior Tecnico,́ Universidade de Lisboa, Avenida Rovisco Pais, 1049-001, Lisbon, Portugal § Hovione FarmaCiencia SA, R&D, Sete Casas, 2674-506, Loures, Portugal *S Supporting Information 4.1.1. Altering the Synthesis AC 4.1.2. Adjusting Reaction Conditions To Miti- gate GTI Formation AC 4.1.3. Quality by Design AE 4.2. API Purification AF 4.2.1. Purge Factors AF 4.2.2. Separation Technologies AG 5. Conclusions and Future Trends AL Associated Content AM Supporting Information AM Author Information AM Corresponding Authors AM Notes AM CONTENTS Biographies AM Acknowledgments AN 1. Introduction A References AN 2. Genotoxicity: Mechanisms, Risk and Regulation C 3. Chemical Classes of Common Genotoxic Impur- ities E 1. INTRODUCTION 3.1. Genotoxic Compounds Used as Reactants F Most pharmaceutical products are manufactured either by 3.1.1. Alkyl Halides F applying a total synthesis approach or by modifying a naturally 3.1.2. Dialkyl Sulfates I occurring product. In both cases, a wide range of reactive 3.1.3. Epoxides K reagents are used. Therefore, it is natural that low levels of such 3.1.4. Hydrazines L reagents or side products are present in the final active 3.1.5. TEMPO N pharmaceutical ingredient (API) or drug product as impurities.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2005/0054688A1 May Et Al
    US 2005.0054688A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0054688A1 May et al. (43) Pub. Date: Mar. 10, 2005 (54) SELECTIVE SEROTONN REUPTAKE Related U.S. Application Data INHIBITORS IN THE TREATMENT OF DISEASE (60) Provisional application No. 60/528,136, filed on Dec. 9, 2003. (75) Inventors: Kathryn Elizabeth May, County of Kent (GB); Paul Quinn, County of (30) Foreign Application Priority Data Kent (GB) Aug. 8, 2003 (GB)......................................... O3187O6.9 Correspondence Address: PFIZER INC. Publication Classification PATENT DEPARTMENT, MS8260-1611 EASTERN POINT ROAD (51) Int. Cl." ......................... A61K 31/44; A61K 31/18; GROTON, CT 06340 (US) A61K 31/137 (52) U.S. Cl. ........................... 514/345; 514/602; 514/649 (73) Assignee: Pfizer Inc (57) ABSTRACT (21) Appl. No.: 10/911,806 The present invention provides the use of Selective Serotonin reuptake inhibitors (SSRIs) to treat premature female (22) Filed: Aug. 5, 2004 Orgasm. US 2005/0054688A1 Mar. 10, 2005 SELECTIVE SEROTONIN REUPTAKE 0009 b) Interpersonal difficulties arise from female INHIBITORS IN THE TREATMENT OF DISEASE lack of motivation for/discomfort with continued Sexual Stimulation. 0001. This application claims priority from United King dom Application Number 0318706.9, filed on Aug. 8, 2003 0010 c) The disturbance gives rise to negative psy and the benefit of U.S. Provisional Application No. 60/528, chosocial consequences where arousal occurs in 136, filed on Dec. 9, 2003. inappropriate situations 0002 This invention relates to the use of compounds 0011 d) The disturbance itself causes marked dis which exhibit activity as Selective Serotonin re-uptake treSS or interpersonal difficulty inhibitors (SSRIs) to treat premature female orgasm, and to 0012.
    [Show full text]
  • WHO Drug Information Vol
    WHO Drug Information Vol. 16, No. 1, 2002 World Health Organization WHO Drug Information Contents Vaccines and Biomedicines Hua Fo: unknown substance 26 Sibutramine safety review 26 International reference materials for Cyproterone with ethinylestradiol: risk of Creutzfeldt-Jakob disease 3 venous thromboembolism 27 WHO position on rabies vaccine 4 Alfa interferons: labelling change 27 Nefazodone: rare cases of liver failure 28 Safety Information Acarbose, zafirlukast and vincristine: WHO international drug monitoring: revised precautions 28 cerivastatin and gemfibrozil 8 Clozapine and myocarditis 28 International Conference on Harmonization Methotrexate: interactions 29 (ICH): pharmacovigilance activities 11 Stavudine: neuromuscular weakness 29 The COX-2 inhibitors 12 Recommended influenza virus vaccine Amiodarone and pulmonary toxicity 14 composition 29 Alendronate: link with pancreatitis? 14 Sodium phosphate oral solution: electrolyte Endocrinotoxicity induced by Coriandrum balance disturbance 30 sativa: a case report 15 Haemolysis after consumption of Viola tricolor 15 Lipodystrophy syndrome under-reported 16 Quality Assurance Issues WHO pilot pre-qualification project for pharmaceutical products: evaluation Current Topics of product files 31 Progress in pharmacogenetics and Access to HIV drugs and diagnostics 31 pharmacogenomics 17 List of pre-qualified products — 20 March 2002 32 Internet sales and reimbursement by insurance companies 20 Nevirapine: comments on HIVNET 012 from Recent Publications and Sources the manufacturer 21 Review
    [Show full text]
  • Rana Dadashova
    University of Alberta Is Atomoxetine effective in treating nicotine withdrawal? A double-blind, placebo-controlled, fixed-dose study by Rana Dadashova A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science Department of Psychiatry ©Rana Dadashova Fall 2011 Edmonton, Alberta Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission. Dedication This work is dedicated to my lovely husband Mehti Dadashov and my dear children Seymur and Kamilla, whose love, inspiration and great support made this project successful. I also dedicate these theses to my dear parents Vera Stadnik and Valeriy Stadnik, whose deepest love and couching has been navigating me throughout my life. Abstract Drugs that affect noradrenaline neurotransmission are used as therapy for smoking cessation. A recent study in individuals with attention-deficit and hyperactivity disorder (ADHD) suggested that atomoxetine, a noradrenaline reuptake inhibitor, may reduce cravings in individuals with ADHD who also smoked. The present double-blind, placebo-controlled, fixed-dose study investigated the effect of atomoxetine on nicotine withdrawal in otherwise healthy smokers, who has no psychiatric condition, and wish to stop smoking.
    [Show full text]