DOCSLIB.ORG

(8) Field of Styligi C.E.O. M. Eitan

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(8) Field of Styligi C.E.O. M. Eitan USOO6514482B1 (12) United States Patent (10) Patent No.: US 6,514,482 B1 Bartus et al. (45) Date of Patent: Feb. 4, 2003 (54) PULMONARY DELIVERY IN TREATING 5,985,309 A 11/1999 Edwards et al. ............ 424/426 DSORDERS OF THE CENTRAL NERVOUS 6,019.968 A 2/2000 Platz et al. .............. 424/130.1 SYSTEM 6,048.857 A 4/2000 Ellinwood, Jr. et al. ... 514/221 6,103.270 A 8/2000 Johnson et al. ............. 424/489 (75) Inventors: Raymond T. Bartus, Sudbury, MA 6,136.295 A 10/2000 Edwards et al. .............. 424/45 (US); Dwaine F. Emerich, C t RI 6,165,463 A 12/2000 Platz et al. .............. 424/130.1 (US , UranSLOn, 6,193.954 B1 * 2/2001 Adjei et al. ................... 424/45 FOREIGN PATENT DOCUMENTS (73) Assignee: Advanced Inhalation Research, Inc., CA 2152684 6/1995 Cambridge, MA (US) EP O 496 307 A1 7/1992 (*) Notice: Subject to any disclaimer, the term of this wo WO E. E. patent is extended or adjusted under 35 WO WO 98/31346 7/1998 U.S.C. 154(b) by 0 days. WO WO 98/46245 10/1998 WO WO OO/72827 A2 12/2000 (21) Appl. No.: 09/665,252 WO WO 01/95874 A2 12/2001 (22) Filed: Sep. 19, 2000 OTHER PUBLICATIONS (51) Int. Cl. ............................ A61K 9/12, A61K 9/14, Journal of the Neurological Sciences, Vol. 150, Issue: 1001, s A61 K 9.75 supplement 1, p. S198, Sep. 1997.* (52) U.S. Cl. ........................... 424/45; 424/43; 424/789; * cited by examiner (8) Field of Styligi514/220; 128/203.15 C.E.O. M. Eitan s s s • -u- as (74) Attorney, Agent, or Firm-Hamilton, Brook, Smith & (56) References Cited Reynolds, P.C. U.S. PATENT DOCUMENTS (57) ABSTRACT 4.814.161 A 3/1989 Jinks et all 424/45 A method of pulmonary delivery of a medicament, for 4805710. A 1900 Radhakrishnana". 424/4s example a dopamine precursor or a dopamine agonist, which 5,118,494. A 6/1992 Schultz et al. ................ 424/45 includes administering to the respiratory tract of a patient in 5,166,202 A 11/1992 Schweizer .................. 514/220 need of rescue therapy particles comprising an effective 5,284,133 A 2/1994 Burns et al. ...... 128/200.23 amount of a medicament. The particles are delivered to the 5,354.885. A * 10/1994 Millman et al. .............. 560/43 pulmonary System and are released into the blood Stream 5,457,100 A : 10/1995 Daniel .............. ... 514/220 and delivered to the medicament's Site of action in a time 5. E. A . g s et l, - - - - - - - - - - - - - - 3.i. Sufficiently short to provide the rescue therapy. In addition to 5756,071 A E. MNN .. - - - - - - i.f45 the medicament, the particles can include other materials 5855,913 A 1/1999 Hanes et all - - - - - - - - - - - - - - - -424/489 Such as, for example, phospholipids, amino acids, combi 5.874.064 A 2/1999 Edwards et al... 424/46 nations thereof and others. Preferred particles have a tap 5,875,776 A 3/1999 Vaghefi ............ ... 128/203.15 density of less than about 0.4 g/cm. 5,922,354 A 7/1999 Johnson et al. ............. 424/489 5,981,474. A 11/1999 Manning et al. ............... 514/2 42 Claims, 9 Drawing Sheets O 10 20 30 40 SO 80 time (minutes) C) 0. 2O 30 40 .50 SC time minutes) U.S. Patent Feb. 4, 2003 Sheet 1 of 9 US 6,514,482 B1 3OOO 25OO 2OOO 5OO OOO time (minutes) FG. A 28OO > J 24OO -- lung St - -o- - Oro S 2OOO O 5 6.OO E i2OO o Cl O a 8OO - b C O time (minutes) FIG. B U.S. Patent Feb. 4, 2003 Sheet 2 of 9 US 6,514,482 B1 5OOO --O-- Lung Administration -- Oro Administration 4OOO 3OOO 2OOO 1 OOO BOSeine 2 min 15 m in 45 min FIG. 2A ---O--- Lung Administration 6- OO -- Oro AdministrOtion 5OO 4OO 3OO Bose line 2 min 15 min 45 min FIG. 2B U.S. Patent Feb. 4, 2003 Sheet 3 of 9 US 6,514,482 B1 -- blood-lung 25 -0- striatum lung --D-- blood-ord --O-- Striotum Oro 20 CfO N 3t E 5 N O t up O - i--------------- - - - - C d O st 5 O O min 2 min 5 min 5 min 4 2 -o- Oro n = 5 -O- Tracheotomy n = 9 E old -- Ventilator n = 9 N 2 8 2 9 6 GB 4 pre 2 m in 5 min 5 min Time Post-Administration (minutes) FIG. 4 U.S. Patent Feb. 4, 2003 Sheet 5 of 9 US 6,514,482 B1 Olfactory Occipital Strid to Fronto HPC Cerebellum F.G. 6A 2 ZZ 1 % O.5 % O-Fe- % Olfactory Occipitol Strid to FrontC HPC Cerebellum F.G. 6B U.S. Patent Feb. 4, 2003 Sheet 6 of 9 US 6,514,482 B1 6OOO O IV (n = 6) e 5OOO. Lung (n = 6) S s 4OOO s C 3OOO dis ce 20OO c V 1 OOO Kidney Spleen Heart Testes Muscle Blood FIG. 7A Kidney Spleen Heart Testes Muscle FG. 7B U.S. Patent Feb. 4, 2003 Sheet 7 of 9 US 6,514,482 B1 25OOO 2OOOO Pulmonary c)E 15OOO 9 N. S - to - a9 S.8 10OOO O ae (d CE 5OOO Oro O O 5 1O 15 2O 25 3O Time Post-Drug Administration (minutes) O - x * 8 Txx -e- Oro --e-- Pulmonary U.S. Patent Feb. 4, 2003 Sheet 8 of 9 US 6,514,482 B1 3. 2.5 O P 2 -as 5 1.5 d Ol S S. d O Integrate: O5 Ared Under Curve = 11, 1423 O 2 4. 6 8 1O Time (hours) FIG. O U.S. Patent Feb. 4, 2003 Sheet 9 of 9 US 6,514,482 B1 1O 6 Integrate: Ared Under Curve = 19.9237 Time (hours) FIG. US 6,514,482 B1 1 2 PULMONARY DELIVERY IN TREATING epilepsy) is approximately 250,000. A significant number of DSORDERS OF THE CENTRAL NERVOUS patients also Suffer from So-called “cluster Seizures', SYSTEM wherein an initial Seizure forewarns that a Series of addi tional Seizures will occur within a relatively short time frame. By some reports, 75% of all patients continue to BACKGROUND OF THE INVENTION experience Seizures despite taking medication chronically. Poor compliance with the prescribed medications is believed Parkinson's disease is characterized neuropathologically to be a significant (albeit not Sole) contributing factor. The by degeneration of dopamine neurons in the basal ganglia importance of controlling or minimizing the frequency and and neurologically by debilitating tremors, SlowneSS of intensity of Seizures lies in the fact that incidence of Seizures movement and balance problems. It is estimated that over has been correlated with neuronal deficits and is believed to one million people suffer from Parkinson's disease. Nearly cause loSS of neurons in the brain. all patients receive the dopamine precursor levodopa or Despite chronic treatment, as many as 75% of all patients L-Dopa, often in conjunction with the dopa-decarboxylase continue to exhibit periodic Seizures. The uncontrolled Sei inhibitor, carbidopa. L-Dopa adequately controls Symptoms Zures occur in many forms. In the case of “cluster Seizures,” of Parkinson's disease in the early Stages of the disease. 15 one Seizure Serves notice that a cascade has begun which However, it tends to become less effective after a period will lead to a Series of Seizures before the total episode which can vary from Several months to Several years in the passes. In certain patients, prior to the onset of a Severe course of the disease. Seizure, Some Subjective feeling or Sign is detected by the It is believed that the varying effects of L-Dopa in patient (defined as an aura). In both instances, an opportu Parkinson's disease patients is related, at least in part, to the nity exists for these patients to Significantly reduce the plasma half life of L-Dopa which tends to be very short, in liability of the seizure through “self medication'. While the range of 1 to 3 hours, even when co-administered with many patients are instructed to do So, the drugs currently carbidopa. In the early Stages of the disease, this factor is available to permit effective self medication are limited. mitigated by the dopamine Storage capacity of the targeted 25 Panic attacks purportedly affect about 2.5 million people striatal neurons. L-Dopa is taken up and Stored by the in this country alone. The disorder is characterized by acute neurons and is released over time. However, as the disease episodes of anxiety, leading to difficult breathing, dizziness, progresses, dopaminergic neurons degenerate, resulting in heart palpitations and fear of losing control. The disorder is decreased dopamine Storage capacity. Accordingly, the posi believed to involve a problem with the sympathetic nervous tive effects of L-Dopa become increasingly related to fluc System (involving an exaggerated arousal response, leading tuations of plasma levels of L-Dopa. In addition, patients to overstimulation of adrenaline release and/or adrenergic tend to develop problems involving gastric emptying and neurons). Benzodiazepines are effective against these poor intestinal uptake of L-Dopa. Patients exhibit increas attackS. ingly marked Swings in Parkinson's disease Symptoms, A pure vasogenic etiology/pathogenesis for migraine was ranging from a return to classic Parkinson's disease 35 first proposed in the 1930s; by the 1980s, this was replaced Symptoms, when plasma levels fall, to the So-called by a neurogenic etiology/pathogenesis, which temporarily dyskinesis, when plasma levels temporarily rise too high won favor among migraine investigators.
Load more

Recommended publications
  • 1,4-Benzodiazepine: an Overview of Biological Properties
    Sci. Revs. Chem. Commun.: 5(1), 2015, 13-20 ISSN 2277-2669 1,4-BENZODIAZEPINE: AN OVERVIEW OF BIOLOGICAL PROPERTIES IRAM KHAN*, ANUPAMA and BHAWANI SINGHa Department of Chemistry, Banasthali University, BANASTHALI (Raj.) INDIA aDepartment of Pure & Applied Chemistry, University of Kota, KOTA (Raj.) INDIA (Received : 16.02.2015; Accepted : 02.03.2015) ABSTRACT The term benzodiazepine is the chemical name for the heterocyclic ring system, which is a fusion of benzene and diazepine ring systems. 1,4-benzodiazepine is related with a huge range of biological properties. These ring systems are incorporated into drugs used for AIDS, cancer, anti-viral treatment etc. 1,4-benzodiazepine derivatives are well established in the literature as important biologically active compounds. They have a long history of application in agrochemicals and pharmaceutical industry as herbicides and active pharmaceuticals. 1,4-benzodiazepine and their numerous derivatives have continued to capture the concentration of chemists since their existence in the biologically active materials have been known to produce additive effect on the bio-efficacy of the molecules. Key words: 1,4-benzodiazepine, anti-viral, bio-efficacy. INTRODUCTION History of benzodiazepines was started after the discovery of diazepam (Fig. 1) in 1955 by Leo Sternbach. From that day the research on 1,4- benzodiazepine nucleus is continue. There is a lots of drugs having 1,4-benzodiazepine nucleus. 1,4-Benzodiazepine nucleus containing drugs mostly used for the treatment of anxiety, but they also are useful in treating several other conditions in human. It is a most common prescribed drug for CNS disorders. Benzodiazepines affect a neurotransmitter chemical, gamma- aminobutyric acid (GABA), which is used by nerves to communicate with one another1.
    [Show full text]
  • Treatments for Spasticity and Pain in Multiple Sclerosis: a Systematic Review
    This is a repository copy of Treatments for spasticity and pain in multiple sclerosis: a systematic review . White Rose Research Online URL for this paper: http://eprints.whiterose.ac.uk/1776/ Monograph: Beard, S.M., Hunn, A. and Wight, J. (2003) Treatments for spasticity and pain in multiple sclerosis: a systematic review. Technical Report. Gray Publishing , Tunbridge Wells. ISSN 1366-5278 Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version - refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher’s website. Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. [email protected] https://eprints.whiterose.ac.uk/ Health Technology Assessment 2003; Vol. 7: No. 40 Treatments for spasticity and pain in multiple sclerosis: a systematic review S Beard A Hunn J Wight Health Technology Assessment NHS R&D HTA Programme HTA HTA How to obtain copies of this and other HTA Programme reports. An electronic version of this publication, in Adobe Acrobat format, is available for downloading free of charge for personal use from the HTA website (http://www.ncchta.org).
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2009/0005722 A1 Jennings-Spring (43) Pub
    US 20090005722A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0005722 A1 Jennings-Spring (43) Pub. Date: Jan. 1, 2009 (54) SKIN-CONTACTING-ADHESIVE FREE Publication Classification DRESSING (51) Int. Cl. Inventor: Barbara Jennings-Spring, Jupiter, A61N L/30 (2006.01) (76) A6F I3/00 (2006.01) FL (US) A6IL I5/00 (2006.01) Correspondence Address: AOIG 7/06 (2006.01) Irving M. Fishman AOIG 7/04 (2006.01) c/o Cohen, Tauber, Spievack and Wagner (52) U.S. Cl. .................. 604/20: 602/43: 602/48; 4771.5; Suite 2400, 420 Lexington Avenue 47/13 New York, NY 10170 (US) (57) ABSTRACT (21) Appl. No.: 12/231,104 A dressing having a flexible sleeve shaped to accommodate a Substantially cylindrical body portion, the sleeve having a (22) Filed: Aug. 29, 2008 lining which is substantially non-adherent to the body part being bandaged and having a peripheral securement means Related U.S. Application Data which attaches two peripheral portions to each other without (63) Continuation-in-part of application No. 1 1/434,689, those portions being circumferentially adhered to the sleeve filed on May 16, 2006. portion. Patent Application Publication Jan. 1, 2009 Sheet 1 of 9 US 2009/0005722 A1 Patent Application Publication Jan. 1, 2009 Sheet 2 of 9 US 2009/0005722 A1 10 8 F.G. 5 Patent Application Publication Jan. 1, 2009 Sheet 3 of 9 US 2009/0005722 A1 13 FIG.6 2 - Y TIII Till "T fift 11 10 FIG.7 8 13 6 - 12 - Timir" "in "in "MINIII.
    [Show full text]
  • Touchpoints for Addressing Substance Use Issues in Home Visiting: Phase 1 Final Report OPRE Report 2020-27 March 2020
    Anchor Touchpoints for Addressing Substance Use Issues in Home Visiting: Phase 1 Final Report OPRE Report 2020-27 March 2020 This page has been left blank for double-sided copying. Touchpoints for Addressing Substance Use Issues in Home Visiting: Phase 1 Final Report OPRE Report 2020-27 March 2020 Mynti Hossain, Lauren Akers, Patricia Del Grosso, Marisa Shenk, Michael Cavanaugh, and Melissa Azur Submitted to: Nicole Denmark, Project Officer Office of Planning, Research, and Evaluation Administration for Children and Families U.S. Department of Health and Human Services Contract Number: HHSP233201500035I Submitted by: Mathematica P.O. Box 2393 Princeton, NJ 08543-2393 Telephone: (609) 799-3535 Project Director: Patricia Del Grosso This report is in the public domain. Permission to reproduce is not necessary. Suggested citation: Hossain, Mynti, Akers, Lauren, Del Grosso, Patricia, Shenk, Marisa, Cavanaugh, Michael, and Azur, Melissa (2020). Touchpoints for Addressing Substance Use Issues in Home Visiting: Phase 1 Final Report, OPRE Report # 2020-27. Washington, DC: Office of Planning, Research, and Evaluation, Administration for Children and Families, U.S. Department of Health and Human Services. Disclaimer: The views expressed in this publication do not necessarily reflect the views or policies of the Office of Planning, Research, and Evaluation, the Administration for Children and Families, or the U.S. Department of Health and Human Services. This report and other reports sponsored by the Office of Planning, Research, and Evaluation are available at http://www.acf.hhs.gov/opre. Sign-up for the OPRE Newsletter Follow OPRE on Like OPRE on Facebook Follow OPRE on Twitter @OPRE_ACF facebook.com/OPRE.ACF Instagram@opre_acf This page has been left blank for double-sided copying.
    [Show full text]
  • Mental Disorders and Illicit Drug Use Expert Group
    Global Burden of Disease Mental Disorders and Illicit Drug Use Expert Group Fiona Charlson, Louisa Degenhardt, Jennifer McLaren, Wayne Hall and Michael Lynskey Benzodiazepine-related mortality Illicit Drugs Discussion Paper No. 1 GBD2005 Mental Disorders and Illicit Drug Use Expert Group www.gbd.unsw.edu.au BENZODIAZEPINE-RELATED MORTALITY Fiona Charlson, Louisa Degenhardt, Jennifer McLaren, Wayne Hall and Michael Lynskey Illicit Drugs Discussion Paper No. 1 Recommended citation: Charlson, F., Degenhardt, L., McLaren, J., Hall, W., & Lynskey, M. (2008). Benzodiazepine- related mortality. Global Burden of Disease Mental Disorders and Illicit Drug Use Expert group, Illicit drugs discussion paper No. 1. National Drug and Alcohol Research Centre, University of NSW: Sydney. ISBN: 978 0 7334 2688 9 ©NATIONAL DRUG AND ALCOHOL RESEARCH CENTRE, UNIVERSITY OF NEW SOUTH WALES, SYDNEY, 2008 This work is copyright. You may download, display, print and reproduce this material in unaltered form only (retaining this notice) for your personal, non-commercial use or use within your organisation. All other rights are reserved. Requests and enquiries concerning reproduction and rights should be addressed to the information manager, National Drug and Alcohol Research Centre, University of New South Wales, Sydney,NSW 2052, Australia. GBD2005 Mental Disorders and Illicit Drug Use Expert Group www.gbd.unsw.edu.au Table of contents Summary and recommendations .............................................................................................. 1 1. Introduction
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2002/0102215 A1 100 Ol
    US 2002O102215A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2002/0102215 A1 Klaveness et al. (43) Pub. Date: Aug. 1, 2002 (54) DIAGNOSTIC/THERAPEUTICAGENTS (60) Provisional application No. 60/049.264, filed on Jun. 6, 1997. Provisional application No. 60/049,265, filed (75) Inventors: Jo Klaveness, Oslo (NO); Pal on Jun. 6, 1997. Provisional application No. 60/049, Rongved, Oslo (NO); Anders Hogset, 268, filed on Jun. 7, 1997. Oslo (NO); Helge Tolleshaug, Oslo (NO); Anne Naevestad, Oslo (NO); (30) Foreign Application Priority Data Halldis Hellebust, Oslo (NO); Lars Hoff, Oslo (NO); Alan Cuthbertson, Oct. 28, 1996 (GB)......................................... 9622.366.4 Oslo (NO); Dagfinn Lovhaug, Oslo Oct. 28, 1996 (GB). ... 96223672 (NO); Magne Solbakken, Oslo (NO) Oct. 28, 1996 (GB). 9622368.0 Jan. 15, 1997 (GB). ... 97OO699.3 Correspondence Address: Apr. 24, 1997 (GB). ... 9708265.5 BACON & THOMAS, PLLC Jun. 6, 1997 (GB). ... 9711842.6 4th Floor Jun. 6, 1997 (GB)......................................... 97.11846.7 625 Slaters Lane Alexandria, VA 22314-1176 (US) Publication Classification (73) Assignee: NYCOMED IMAGING AS (51) Int. Cl." .......................... A61K 49/00; A61K 48/00 (52) U.S. Cl. ............................................. 424/9.52; 514/44 (21) Appl. No.: 09/765,614 (22) Filed: Jan. 22, 2001 (57) ABSTRACT Related U.S. Application Data Targetable diagnostic and/or therapeutically active agents, (63) Continuation of application No. 08/960,054, filed on e.g. ultrasound contrast agents, having reporters comprising Oct. 29, 1997, now patented, which is a continuation gas-filled microbubbles stabilized by monolayers of film in-part of application No. 08/958,993, filed on Oct.
    [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]
  • WO 2016/066256 Al 6 May 2016 (06.05.2016) W P O P C T
    (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 WO 2016/066256 Al 6 May 2016 (06.05.2016) W P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 9/06 (2006.01) A61K 47/38 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 47/14 (2006.01) A61K 47/44 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (21) International Application Number: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/EP20 15/0021 17 HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (22) International Filing Date: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, 26 October 2015 (26.10.201 5) MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (25) Filing Language: English SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (26) Publication Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 1419257. 29 October 2014 (29. 10.2014) GB kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, (71) Applicant: JAGOTEC AG [CH/CH]; Eptingerstrasse 61, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, CH-4132 Muttenz (CH).
    [Show full text]
  • Benzodiazepines, the Story of the Antagonist Flumazenil and of the Partial Agonist Bretazenil
    FORSCHUNG 141 (,HIMIA 47 (1993) Nr." (Mai) Chim;a 47 (/993) 141-/47 © Neue SchIVeizerische Chemische Gesellscllllft /SSN 0009-4293 Benzodiazepines, the Story of the Antagonist Flumazenil and of the Partial Agonist Bretazenil Walter Hunkeler: Born 1938 in Altishofen. Walter Hunkeler* Lucerne. 1955-58 apprenticeship as laborato- ry assistentatS;egfr;edAG inZofingen. 1960- 63 study of chemistry at the Institute of Tech- nology of the State of Berne. Burgdorf. and Abstract. The story offlumazenil and bretazenil is a typical example of a serendipitious 1965-69 at the University of Berne. Doctoral drug discovery. In 1979 benzodiazepine antagonists were unknown. No one was thesis under the direction of Prof. H. Sclwlteg- looking for them, but they were discovered nevertheless. Ro 15-1788 was selected for ger. Postdoctoral research at the ETH-Zurich with Prof. A. Eschenmoser. Since 1974 at F. clinical trial. Today 'this compound has the generic name f1umazenil, the trade name Hoffmann-La Roche AG in Basel. Anexate, and is registered in 70 countries. Itis the first specific benzodiazepine receptor antagonist for clinical use. Minor structural modifications of benzodiazepine antago- nists led to partial agonists, compounds with powerful anxiolytic and anticonvulsant properties. Compared with full agonists they have markedly reduced sedative and alcohol-potentiating effects. Bretazenil is in clinical trial; it exhibits promising anxio- other stems from the triazolobenzo-di- lytic activity especially in patients with panic attacks. In open clinical studies it has azepines, which were synthesized and in- shown remarkable antipsychotic activity. Structure-activity relationships and spin-offs vestigated at about the same time at Take- are discussed.
    [Show full text]
  • Prospective Memory and Future Event Simulation in Frequent Cannabis Users
    Prospective Memory and Future Event Simulation in Frequent Cannabis Users Ruth Braidwood DClinPsy Thesis (Volume 1), 2017 University College London UCL Doctorate in Clinical Psychology Thesis declaration form I confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. Signature: Name: Ruth Braidwood Date: 1 Overview Part one of this major research project is a systematic review of the evidence for cognitive remediation for adults with substance use disorders (SUDs). Given the clinical heterogeneity across the 15 included studies (in terms of intervention characteristics, outcome measures used, and quality of reporting), a narrative approach was used to synthesize results. Although there was some evidence for the intervention improving some cognitive and substance use outcomes, this was not consistent, and the review highlights the lack of robust evidence for cognitive remediation for adults with SUDs. Suggestions for future research are discussed. Part two is an empirical paper describing a study to assess the effects of frequent cannabis use on prospective memory. Prospective memory was assessed using the Virtual Week task over three groups: dependent cannabis users, non- dependent cannabis users and non-using controls. There were no differences found between groups. The introduction of an imagining technique whereby participants had to imagine performing their prospective memory tasks during encoding did not improve prospective memory performance for any of the groups. The results raise important questions about the cognitive effects of cannabis use, and interpreting the findings of this study in light of the strengths and limitations of the research.
    [Show full text]
  • ― D03 - 1 ― 医学中央雑誌刊行会・医学用語シソーラス 第9版（ 2019） カテゴリー別リスト
    医学中央雑誌刊行会・医学用語シソーラス 第9版（ 2019） カテゴリー別リスト 複素環式化合物 D03+ Alkaloids D03-10+ Aconitine D03-10-10 # Acridones D03-10-20+ # Acronine D03-10-20-10 # Amaryllidaceae Alkaloids D03-10-30+ Galantamine D03-10-30-10 # Anabasine D03-10-40 # Arecoline D03-10-50 # Benzophenanthridines D03-10-60 # Benzylisoquinolines D03-10-70+ # Aporphines D03-10-70-10+ # Apomorphine D03-10-70-10-10 # Berberine Alkaloids D03-10-70-20+ # Berberine D03-10-70-20-10 # Bicuculline D03-10-70-30 # * Cepharanthine D03-10-70-40 # Papaverine D03-10-70-50+ # Drotaverin D03-10-70-50-10 # Ethaverine D03-10-70-50-20 # Tetrahydropapaveroline D03-10-70-50-30 # Toxiferine D03-10-70-60+ # Alcuronium D03-10-70-60-10 # Tubocurarine D03-10-70-70+ # Dimethyltubocurarinium Chloride D03-10-70-70-10 # Betalains D03-10-80+ # Betacyanins D03-10-80-10 # Betaxanthins D03-10-80-20 # Camptothecin D03-10-90+ # Belotecan D03-10-90-10 # Diflomotecan D03-10-90-20 # Exatecan D03-10-90-30 # Irinotecan D03-10-90-40 # Rubitecan D03-10-90-50 # Topotecan D03-10-90-60+ # Delimotecan D03-10-90-60-10 # Cinchona Alkaloids D03-10-100+ Quinidine D03-10-100-10 # Quinine D03-10-100-20 # Colchicine D03-10-110+ # Demecolcine D03-10-110-10 # Lumicolchicines D03-10-110-20 1-Deoxynojirimycin D03-10-120+ # Emiglitate D03-10-120-10 # * Migalastat D03-10-120-20 # Miglitol D03-10-120-30 # Miglustat D03-10-120-40 # Dihydro-Beta-Erythroidine D03-10-130 # Emetine D03-10-140+ # Dehydroemetine D03-10-140-10 # Ergot Alkaloids D03-10-150+ Ergolines D03-10-150-10+ # Cabergoline D03-10-150-10-10 # Ergonovine D03-10-150-10-20+ # Methylergometrine
    [Show full text]
  • Touchpoints for Addressing Substance Use Issues in Home Visiting: Phase 1 Final Report OPRE Report 2020-27 March 2020
    Anchor Touchpoints for Addressing Substance Use Issues in Home Visiting: Phase 1 Final Report OPRE Report 2020-27 March 2020 This page has been left blank for double-sided copying. Touchpoints for Addressing Substance Use Issues in Home Visiting: Phase 1 Final Report OPRE Report 2020-27 March 2020 Mynti Hossain, Lauren Akers, Patricia Del Grosso, Marisa Shenk, Michael Cavanaugh, and Melissa Azur Submitted to: Nicole Denmark, Project Officer Office of Planning, Research, and Evaluation Administration for Children and Families U.S. Department of Health and Human Services Contract Number: HHSP233201500035I Submitted by: Mathematica P.O. Box 2393 Princeton, NJ 08543-2393 Telephone: (609) 799-3535 Project Director: Patricia Del Grosso This report is in the public domain. Permission to reproduce is not necessary. Suggested citation: Hossain, Mynti, Akers, Lauren, Del Grosso, Patricia, Shenk, Marisa, Cavanaugh, Michael, and Azur, Melissa (2020). Touchpoints for Addressing Substance Use Issues in Home Visiting: Phase 1 Final Report, OPRE Report # 2020-27. Washington, DC: Office of Planning, Research, and Evaluation, Administration for Children and Families, U.S. Department of Health and Human Services. Disclaimer: The views expressed in this publication do not necessarily reflect the views or policies of the Office of Planning, Research, and Evaluation, the Administration for Children and Families, or the U.S. Department of Health and Human Services. This report and other reports sponsored by the Office of Planning, Research, and Evaluation are available at http://www.acf.hhs.gov/opre. This page has been left blank for double-sided copying. ACKNOWLEDGMENTS We would like to express our appreciation to our Project Officer Nicole Denmark (Office of Planning, Research, and Evaluation [OPRE]).
    [Show full text]