DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 9,005,660 B2 Tygesen Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 9,005,660 B2 Tygesen Et Al USOO9005660B2 (12) United States Patent (10) Patent No.: US 9,005,660 B2 Tygesen et al. (45) Date of Patent: Apr. 14, 2015 (54) IMMEDIATE RELEASE COMPOSITION 4,873,080 A 10, 1989 Bricklet al. RESISTANT TO ABUSEBY INTAKE OF 4,892,742 A 1, 1990 Shah 4,898,733. A 2f1990 DePrince et al. ALCOHOL 5,019,396 A 5/1991 Ayer et al. 5,068,112 A 11/1991 Samejima et al. (75) Inventors: Peter Holm Tygesen, Smoerum (DK); 5,082,655 A 1/1992 Snipes et al. Jan Martin Oevergaard, Frederikssund 5,102,668 A 4, 1992 Eichel et al. 5,213,808 A 5/1993 Bar Shalom et al. (DK); Joakim Oestman, Lomma (SE) 5,266,331 A 11/1993 Oshlack et al. 5,281,420 A 1/1994 Kelmet al. (73) Assignee: Egalet Ltd., London (GB) 5,352.455 A 10, 1994 Robertson 5,411,745 A 5/1995 Oshlack et al. (*) Notice: Subject to any disclaimer, the term of this 5,419,917 A 5/1995 Chen et al. patent is extended or adjusted under 35 5,422,123 A 6/1995 Conte et al. U.S.C. 154(b) by 473 days. 5,460,826 A 10, 1995 Merrill et al. 5,478,577 A 12/1995 Sackler et al. 5,508,042 A 4/1996 OShlack et al. (21) Appl. No.: 12/701.248 5,520,931 A 5/1996 Persson et al. 5,529,787 A 6/1996 Merrill et al. (22) Filed: Feb. 5, 2010 5,549,912 A 8, 1996 OShlack et al. 5,593,695 A 1/1997 Merrill et al. (65) Prior Publication Data 5,609,885 A 3, 1997 Rivera et al. 5,614,218 A 3, 1997 Olsson et al. US 2010/0204259 A1 Aug. 12, 2010 5,618,560 A 4/1997 Bar-Shalom et al. 5,656,291 A 8, 1997 Olsson et al. 5,656.295 A 8, 1997 OShlack et al. Related U.S. Application Data 5,667,805 A 9, 1997 Merrill et al. 5,672,360 A 9, 1997 Sackler et al. (60) Provisional application No. 61/151,491, filed on Feb. 5,741,524 A 4/1998 Staniforth et al. 10, 2009, provisional application No. 61/150,577, (Continued) filed on Feb. 6, 2009. FOREIGN PATENT DOCUMENTS (30) Foreign Application Priority Data DE 202006O14131 1, 2007 Feb. 6, 2009 (DK) ................................. 2009 OO190 EP O435,726 8, 1991 (Continued) (51) Int. Cl. A6 IK9/46 (2006.01) OTHER PUBLICATIONS A6 IK 9/16 (2006.01) A6 IK3I/44 (2006.01) Notification of Transmittal of the International Search Report and the A6 IK3I/6 (2006.01) Written Opinion of the International Searching Authority issued Jul. A6 IK3I/485 (2006.01) 8, 2008 in International Application No. PCT/DK2008/000016. A6 IK3I/67 (2006.01) Preliminary Amendment filed Jul. 13, 2009 in co-pending U.S. Appl. A6 IK 9/28 (2006.01) No. 12/523,045. Notification of Transmittal of the International Search Report and the A6 IK9/20 (2006.01) Written Opinion of the International Searching Authority issued Apr. (52) U.S. Cl. 21, 2010 in International Application No. PCT/EP2010/000728. CPC ............. A61 K9/0007 (2013.01); A61 K3I/485 Notification of Transmittal of the International Search Report and the (2013.01); A61 K3I/I67 (2013.01); A61 K Written Opinion of the International Searching Authority issued May 9/2893 (2013.01); A61 K9/2031 (2013.01); 28, 2010 in International Application No. PCT/DK2010/000019. A61 K9/2095 (2013.01); A61 K9/2866 Fischer, et al., “Nonmedical Use of Prescription Opioids: Furthering (2013.01) a Meaningful Research Agenda.” J. Pain. 9:6, 2008 490-493. (58) Field of Classification Search (Continued) USPC ........................... 424/466,495; 514/282, 629 See application file for complete search history. Primary Examiner — Shirley V Gembeh (74) Attorney, Agent, or Firm — Foley & Lardner LLP (56) References Cited U.S. PATENT DOCUMENTS (57) ABSTRACT The present invention relates to immediate release pharma 2,685,553 A 8, 1954 Carroll et al. ceutical compositions for oral administration that are resis 3,835,221 A 9, 1974 Fulberth et al. 3,957,523 A 5, 1976 Ohno et al. tant to abuse by intake of alcohol. In particular, this disclosure 4,034,758 A 7, 1977 Theeuwes provides immediate release pharmaceutical compositions 4,330,338 A 5, 1982 Banker comprising a polyglycol having a molecular weight of from 4.389,393 A 6, 1983 Schor et al. about 900 to about 17,000 daltons, a drug substance, one or 4.404,183 A 9, 1983 Kawata et al. more effervescent agents, and, optionally, one or more disin 4,449,983 A 5, 1984 Cortese et al. 4,503,067 A 3, 1985 Wiedemann et al. tegrants, such that the composition is formulated to be resis 4,686,212 A 8, 1987 Ducatman et al. tant to abuse by intake of alcohol. 4,824,675 A 4/1989 Wong et al. 4,844,984 A 7, 1989 Eckenhoffetal. 13 Claims, 23 Drawing Sheets US 9,005,660 B2 Page 2 (56) References Cited 7,771,707 B2 8, 2010 Hirsh et al. 7,776,314 B2 8/2010 Bartholomaus et al. U.S. PATENT DOCUMENTS 7,842,307 B2 11/2010 Oshlack et al. 7,846,476 B2 12/2010 Oshlack et al. 5,866,161 A 2f1999 Childers et al. 7,883,722 B2 2/2011 Bar-Shalom. 5,866,164 A 2/1999 Kuczynski et al. 7,883,772 B2 2/2011 Pourdeyhimi et al. 5,869,097 A 2/1999 Wong et al. 7,897,080 B2 3, 2011 Yang et al. 5,879,705 A 3, 1999 Heafield et al. 7,906,143 B1 3/2011 Odidi et al. 5,882,682 A 3, 1999 Rork et al. 7,943,174 B2 5, 2011 Oshlack et al. 5,914, 131 A 6, 1999 Merrill et al. 7968,120 B2 62011 Liet al. 5.948,787 A 9, 1999 Merrill et al. 7.972,624 B2 7/2011 Lietal. 5,952,005 A 9, 1999 Olsson et al. 7,981,439 B2 7/2011 Kumar et al. 5,968,551 A 10/1999 Oshlack et al. 8,017,148 B2 9/2011 Sackler 6,046,177 A 4/2000 Stella et al. 8,017,150 B2 9/2011 Yang et al. 6,066,339 A 5, 2000 Stark et al. 8,029,822 B2 10/2011 Faour et al. 6,077,533 A 6, 2000 OShlack et al. 8,075,872 B2 12/2011 Arkenau-Maric et al. 6,077,538 A 6, 2000 Merrill et al. 8, 101,630 B2 1/2012 Kumar et al. 6,103,261 A 8, 2000 Chasin et al. 8, 105,631 B2 1/2012 Kaiko et al. 6,117,453 A 9, 2000 Seth et al. 8, 114,383 B2 2/2012 Bartholomaus et al. 6,143,328 A 11/2000 Heafield et al. 8,114,384 B2 2/2012 Arkenau et al. 6,183,778 B1 2/2001 Conte et al. 8,133,507 B2 3/2012 Yum et al. 6.225.343 B1 5, 2001 Behlet al. 8,142,811 B2 3/2012 Oshlack et al. 6,245.351 B 62001 Nara et al. 8, 147,870 B2 4/2012 Yum et al. 6.245,357 B1 6/2001 Edgren et al. 8,153,152 B2 4/2012 Yum et al. 6,267,981 B1 7/2001 Okamoto et al. 8,168,217 B2 5/2012 Yum et al. 6,267,985 B1 7/2001 Chen et al. 8,173,152 B2 5/2012 Crowley et al. 6,277.384 B1 8/2001 Kaiko et al. 8, 182,836 B2 5/2012 Mehta 6,284.274 B1 9, 2001 Merrill et al. 8, 192,722 B2 6/2012 Arkenau-Maric et al. 6,294,195 B1 9, 2001 Oshlack et al. 8,231,898 B2 7/2012 Oshlack et al. 6,348.216 B1 2/2002 Kushla et al. 8,246,986 B2 8/2012 Cruz et al. 6,375,957 B1 4/2002 Kaiko et al. 8,309,060 B2 11/2012 Bartholomaus et al. 6,383,471 B1 5, 2002 Chen et al. 8.323,889 B2 12/2012 Arkenau-Maric et al. 6,395.299 B1 5/2002 Babich et al. 8,329.720 B1 12/2012 King et al. 6,399,096 B1 6, 2002 Miller et al. 8.337,888 B2 12/2012 Wright et al. 6.403.579 B1 6, 2002 Heller 8.338,444 B1 12/2012 King et al. 6.451848 B1 9/2002 Behlet al. 8,354,124 B2 1/2013 Yum et al. 6.458,772 B1 10/2002 Zhou et al. 8,361,499 B2 1/2013 Oshlack et al. 6,458,824 B1 10/2002 Iwata et al. 8,367,693 B1 2/2013 King et al. 6,475,494 B2 11/2002 Kaiko et al. 8,372.432 B2 2/2013 Han et al. 6,482.437 B2 11/2002 Debregeas et al. 8,377,453 B2 2/2013 Han et al. 6,488.962 B1 12/2002 Berner et al. 8,383,152 B2 2/2013 Janset al. 6,488.963 B1 12/2002 McGinity et al. 8,383,154 B2 2/2013 Bar-Shalom 6,491.945 B1 12/2002 Childers et al. 8,383,155 B2 2/2013 Bar-Shalom 6,517,866 B1 2/2003 Am Ende et al. 8,389,007 B2 3/2013 Wright et al.
Load more

Recommended publications
  • Medicines Regulations 1984 (SR 1984/143)
    Reprint as at 1 July 2014 Medicines Regulations 1984 (SR 1984/143) David Beattie, Governor-General Order in Council At the Government House at Wellington this 5th day of June 1984 Present: His Excellency the Governor-General in Council Pursuant to section 105 of the Medicines Act 1981, and, in the case of Part 3 of the regulations, to section 62 of that Act, His Excellency the Governor-General, acting on the advice of the Minister of Health tendered after consultation with the organisations and bodies that ap- peared to the Minister to be representatives of persons likely to be substantially affected, and by and with the advice and consent of the Executive Council, hereby makes the following regulations. Contents Page 1 Title and commencement 5 Note Changes authorised by subpart 2 of Part 2 of the Legislation Act 2012 have been made in this official reprint. Note 4 at the end of this reprint provides a list of the amendments incorporated. These regulations are administered by the Ministry of Health. 1 Reprinted as at Medicines Regulations 1984 1 July 2014 2 Interpretation 5 Part 1 Classification of medicines 3 Classification of medicines 11 Part 2 Standards 4 Standards for medicines, related products, medical 11 devices, cosmetics, and surgical dressings 5 Pharmacist may dilute medicine in particular case 12 6 Colouring substances [Revoked] 12 Part 3 Advertisements 7 Advertisements not to claim official approval 13 8 Advertisements for medicines 13 9 Advertisements for related products 15 10 Advertisements for medical devices 15 11 Advertisements
    [Show full text]
  • Classification of Medicinal Drugs and Driving: Co-Ordination and Synthesis Report
    Project No. TREN-05-FP6TR-S07.61320-518404-DRUID DRUID Driving under the Influence of Drugs, Alcohol and Medicines Integrated Project 1.6. Sustainable Development, Global Change and Ecosystem 1.6.2: Sustainable Surface Transport 6th Framework Programme Deliverable 4.4.1 Classification of medicinal drugs and driving: Co-ordination and synthesis report. Due date of deliverable: 21.07.2011 Actual submission date: 21.07.2011 Revision date: 21.07.2011 Start date of project: 15.10.2006 Duration: 48 months Organisation name of lead contractor for this deliverable: UVA Revision 0.0 Project co-funded by the European Commission within the Sixth Framework Programme (2002-2006) Dissemination Level PU Public PP Restricted to other programme participants (including the Commission x Services) RE Restricted to a group specified by the consortium (including the Commission Services) CO Confidential, only for members of the consortium (including the Commission Services) DRUID 6th Framework Programme Deliverable D.4.4.1 Classification of medicinal drugs and driving: Co-ordination and synthesis report. Page 1 of 243 Classification of medicinal drugs and driving: Co-ordination and synthesis report. Authors Trinidad Gómez-Talegón, Inmaculada Fierro, M. Carmen Del Río, F. Javier Álvarez (UVa, University of Valladolid, Spain) Partners - Silvia Ravera, Susana Monteiro, Han de Gier (RUGPha, University of Groningen, the Netherlands) - Gertrude Van der Linden, Sara-Ann Legrand, Kristof Pil, Alain Verstraete (UGent, Ghent University, Belgium) - Michel Mallaret, Charles Mercier-Guyon, Isabelle Mercier-Guyon (UGren, University of Grenoble, Centre Regional de Pharmacovigilance, France) - Katerina Touliou (CERT-HIT, Centre for Research and Technology Hellas, Greece) - Michael Hei βing (BASt, Bundesanstalt für Straßenwesen, Germany).
    [Show full text]
  • (19) United States (12) Patent Application Publication (10) Pub
    US 20130289061A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0289061 A1 Bhide et al. (43) Pub. Date: Oct. 31, 2013 (54) METHODS AND COMPOSITIONS TO Publication Classi?cation PREVENT ADDICTION (51) Int. Cl. (71) Applicant: The General Hospital Corporation, A61K 31/485 (2006-01) Boston’ MA (Us) A61K 31/4458 (2006.01) (52) U.S. Cl. (72) Inventors: Pradeep G. Bhide; Peabody, MA (US); CPC """"" " A61K31/485 (201301); ‘4161223011? Jmm‘“ Zhu’ Ansm’ MA. (Us); USPC ......... .. 514/282; 514/317; 514/654; 514/618; Thomas J. Spencer; Carhsle; MA (US); 514/279 Joseph Biederman; Brookline; MA (Us) (57) ABSTRACT Disclosed herein is a method of reducing or preventing the development of aversion to a CNS stimulant in a subject (21) App1_ NO_; 13/924,815 comprising; administering a therapeutic amount of the neu rological stimulant and administering an antagonist of the kappa opioid receptor; to thereby reduce or prevent the devel - . opment of aversion to the CNS stimulant in the subject. Also (22) Flled' Jun‘ 24’ 2013 disclosed is a method of reducing or preventing the develop ment of addiction to a CNS stimulant in a subj ect; comprising; _ _ administering the CNS stimulant and administering a mu Related U‘s‘ Apphcatlon Data opioid receptor antagonist to thereby reduce or prevent the (63) Continuation of application NO 13/389,959, ?led on development of addiction to the CNS stimulant in the subject. Apt 27’ 2012’ ?led as application NO_ PCT/US2010/ Also disclosed are pharmaceutical compositions comprising 045486 on Aug' 13 2010' a central nervous system stimulant and an opioid receptor ’ antagonist.
    [Show full text]
  • List of Union Reference Dates A
    Active substance name (INN) EU DLP BfArM / BAH DLP yearly PSUR 6-month-PSUR yearly PSUR bis DLP (List of Union PSUR Submission Reference Dates and Frequency (List of Union Frequency of Reference Dates and submission of Periodic Frequency of submission of Safety Update Reports, Periodic Safety Update 30 Nov. 2012) Reports, 30 Nov.
    [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]
  • The Effect of the Roots of Empathy Program on the Use of Psychotropic Medications Among Youth in Manitoba
    The effect of the Roots of Empathy program on the use of psychotropic medications among youth in Manitoba by Lindsey Dahl A Thesis submitted to the Faculty of Graduate Studies of The University of Manitoba in partial fulfilment of the requirements of the degree of MASTER OF SCIENCE Department of Community Health Sciences, Rady Faculty of Health Sciences, Max Rady College of Medicine University of Manitoba Winnipeg Copyright © 2017 by Lindsey Dahl Abstract Background: Psychotropic medications prescriptions to youth have increased. Roots of Empathy (ROE) is a social and emotional learning program that may influence the use of psychotropic medication. Methods: Administrative data was analyzed in a matched sample of children who received ROE during 2002/03 to 2012/13. Kaplan-Meier survival curves and Cox proportional hazard models were used to estimate the association between ROE and psychotropic medication dispensations. Results: Few significant differences were observed. Children who received ROE in kindergarten to grade 3 had a lower adjusted hazard for an anxiolytic dispensation. Children who received ROE in grade 7 to 8 had a higher hazard for an antipsychotic dispensation. Males who received the program had an increased hazard for an antipsychotic dispensation. Conclusion: There was no consistent differences in the likelihood of being dispensed a psychotropic medication between children who received ROE and children who did not in Manitoba. ii Acknowledgments I would like to first thank my thesis advisor Dr. Randy Fransoo of the Department of Community Health Sciences, Rady Faculty of Health Sciences, Max Rady College of Medicine at the University of Manitoba. Right from our initial meeting, Dr.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,603,526 B2 Tygesen Et Al
    USOO8603526B2 (12) United States Patent (10) Patent No.: US 8,603,526 B2 Tygesen et al. (45) Date of Patent: Dec. 10, 2013 (54) PHARMACEUTICAL COMPOSITIONS 2008. O152595 A1 6/2008 Emigh et al. RESISTANT TO ABUSE 2008. O166407 A1 7/2008 Shalaby et al. 2008/0299.199 A1 12/2008 Bar-Shalom et al. 2008/0311205 A1 12/2008 Habib et al. (75) Inventors: Peter Holm Tygesen, Smoerum (DK); 2009/0022790 A1 1/2009 Flath et al. Jan Martin Oevergaard, Frederikssund 2010/0203129 A1 8/2010 Andersen et al. (DK); Karsten Lindhardt, Haslev (DK); 2010/0204259 A1 8/2010 Tygesen et al. Louise Inoka Lyhne-versen, Gentofte 2010/0239667 A1 9/2010 Hemmingsen et al. (DK); Martin Rex Olsen, Holbaek 2010, O291205 A1 11/2010 Downie et al. (DK); Anne-Mette Haahr, Birkeroed 2011 O159100 A1 6/2011 Andersen et al. (DK); Jacob Aas Hoellund-Jensen, FOREIGN PATENT DOCUMENTS Frederikssund (DK); Pemille Kristine Hoeyrup Hemmingsen, Bagsvaerd DE 20 2006 014131 1, 2007 (DK) EP O435,726 8, 1991 EP O493513 7, 1992 EP O406315 11, 1992 (73) Assignee: Egalet Ltd., London (GB) EP 1213014 6, 2002 WO WO 89,09066 10, 1989 (*) Notice: Subject to any disclaimer, the term of this WO WO91,040 15 4f1991 patent is extended or adjusted under 35 WO WO95/22962 8, 1995 U.S.C. 154(b) by 489 days. WO WO99,51208 10, 1999 WO WOOOf 41704 T 2000 WO WO 03/024426 3, 2003 (21) Appl. No.: 12/701,429 WO WOO3,O24429 3, 2003 WO WOO3,O24430 3, 2003 (22) Filed: Feb.
    [Show full text]
  • WO 2015/072852 Al 21 May 2015 (21.05.2015) 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 2015/072852 Al 21 May 2015 (21.05.2015) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 36/84 (2006.01) A61K 31/5513 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 31/045 (2006.01) A61P 31/22 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K 31/522 (2006.01) A61K 45/06 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, PCT/NL20 14/050780 KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (22) International Filing Date: MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, 13 November 2014 (13.1 1.2014) PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (25) Filing Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 61/903,430 13 November 2013 (13. 11.2013) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, (71) Applicant: RJG DEVELOPMENTS B.V.
    [Show full text]
  • Alzheimer's Disease Clinical Trials
    Clinical Trial Perspective 5 Clinical Trial Perspective Alzheimer’s disease clinical trials: past failures and future opportunities Clin. Invest. (Lond.) Over a decade has elapsed since the US FDA has approved a medication for Alzheimer’s Roy Yaari*,1,2 & Ann Hake1,2 disease (AD) despite clinical trials of numerous agents over a wide array of mechanisms 1Eli Lilly & Company, Lilly Corporate including neurotransmitter modulation and disease modifying therapy targeting Center, Indianapolis, IN 46285, USA 2Indiana University School of Medicine, amyloid and tau. The failures of clinical trials in AD may be due to inadequate Department of Neurology, Indianapolis, understanding of mechanisms of action and/or poor target engagement; however, IN 46202, USA other factors could include inadequate study design, stage of AD along the continuum *Author for correspondence: studied, inclusion of participants without Alzheimer’s pathology into clinical trials Tel.: +1 317 651 6163 and limited power of endpoint measures. Future studies will need to carefully assess [email protected] these possible shortcomings in design of upcoming trials, especially as the field moves toward studies of disease modifying agents (as opposed to symptomatic treatment) of AD and to patients that are very early in the disease spectrum. Keywords: Alzheimer’s disease • Alzheimer’s disease biomarkers • amyloid • clinical trials • preclinical Alzheimer’s disease • tau US FDA approved medications continue to provide significant, but modest More than three decades ago, the choliner- symptomatic benefit[5–7] . gic hypothesis proposed that degeneration The compound memantine introduced a of cholinergic neurons in the basal fore- second mechanism for symptomatic treat- brain and the associated loss of cholinergic ment of AD into clinical practice.
    [Show full text]
  • Identification of Channels Underlying the M-Like Potassium Current In
    Identification of channeis underiying the M-like potassium current in NG108-15 neurobiastoma-giioma ceiis A thesis submitted for the degree of Doctor of Philosophy University of London by Jennifer Kathleen Hadley Department of Pharmacology University College London Gower Street London WC1E 6BT ProQuest Number: U644085 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest U644085 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Abstract NG108-15 cells express a potassium current resembling the IVI-current found in sympathetic ganglia. I contributed to the identification of the channels underlying this NG108-15 current. I used patch-clamp methodology to characterise the kinetics and pharmacology of the M-like current and of three candidate channel genes, all capable of producing “delayed rectifier” currents, expressed in mammalian cells. I studied two Kvi .2 clones: NGK1 (rat Kvi .2) expressed in mouse fibroblasts, and MK2 (mouse brain Kvi .2) expressed in Chinese hamster ovary (OHO) cells. Kvi.2 showed relatively positive activation that shifted negatively on repeated activation, some inactivation, block by dendrotoxin and various cations, and activation by niflumic acid.
    [Show full text]
  • Oxaceprol Monotherapy Versus Oxaceprol and Glucosamine Combination Therapy for Knee Osteoarthritis
    Original Article ISSN (Print) : 2454-8952 International Journal of Medical and Dental Sciences, Vol 9(2), DOI: 10.18311/ijmds/2020/24871, July 2020 ISSN (Online) : 2320-1118 Oxaceprol Monotherapy versus Oxaceprol and Glucosamine Combination Therapy for Knee Osteoarthritis Vijay Kumar1, Sanjeev Sareen2, Shrey Bhatia3* 1Professor and Head, Department of Pharmacology, Government Medical College, Patiala – 147001, Punjab, India 2Associate Professor, Department of Orthopaedics, Government Medical College, Patiala – 147001, Punjab, India 3Junior Resident, Department of Pharmacology, Government Medical College, Patiala – 147001, Punjab, India; [email protected] Abstract Introduction: Osteoarthritis (OA) is the commonest form of arthritis which presents with joint pain and functional limitations. Oxaceprol, a derivative of hydroxyproline, inhibits leukocyte migration into the joints thus inhibiting Proline in chondrocytes. Aims and Objective: Glucosamineinflammatory combination process. Oxaceprol therapy also in patients increases diagnosed availability with of Knee Glucosamine Osteoarthritis and improving (KOA). Materials uptake ofand Glucosamine Methods: Thisand To demonstrate efficacy of Oxaceprol Monotherapy versus Oxaceprol and randomly received either Oxaceprol 600mg OD for 4 weeks, or combination of Oxaceprol 600mg OD and Glucosamine was an open labelled, parallel group, Randomized Controlled Trial where 40 adults age ≥50 years diagnosed with KOA visual analogue scale (VAS) recording from baseline to 4 weeks of treatment. Results: Our study showed that both Oxaceprol monotherapySulphate 1500mg (group OD A, for n=20), 4 weeks. and GlucosamineThe patients pluswere Oxaceprol analysed ascombination per the differences therapy (group between B, n=20) WOMAC improved scale scores, joint pain, and stiffness, and functionality as shown by analysing WOMAC scores before, and after 4 weeks of treatment.
    [Show full text]
  • Drugs Influencing Cognitive Function
    Indian J Physiol Phannacol 1994; 38(4) : 241-251 RE\llEW ARTICLE DRUGS INFLUENCING COGNITIVE FUNCTION ALICE KURUYILLA* AND YASUNDARA DEYI Department ofPharmacology. Christian Medical College. Vellore - 632 002 DRUGS INFLUENCING COGNITIVE FUNCTION cerebrovascular disorders with dementias and reversible dementias. Drugs can inOuence cognitive function in several different ways. The cognitrve enhancers or nootropics Primary degenerative disorders include the have become a major issue in drug development during subgroups senile dementia of the Alzheimer's type the last decade. Nootropics arc defined as drugs that (SDAT), Alzheimer's disease, Picks disease and generally increase neuron metabolic activity, improve Huntington's chorea (4). Alzheimer's disease usually cognitive and ,'igilance level and are said to have occurs in individuals past 70 years old and appears to antidemcntia effect (I). These drugs are essential for be in part genetically determin'd (5). the treatment of geriatric disorders like Alzheimer's which have become one of the major problems socially Pathophysiology oj Alzheimer's disease : and medically. Considerable evidence has been gathered Extensive research in the recent years has made major in the last decade to support the observation that advances in understanding the pathogenesis of children with epilepsy have morc learning difficulties Alzheimer's disease (6). The hallmark lesions of than age matched controls (2, 3). Anti-epileptic drugs Alzheimer's disease are neuritic plaques and are useful in controlling the frequency and duration of neurofibrillary tangles. Two amyloid proteins seizures. These drugs can also be the source of side accumulate in Alzheimer's disease, these arc beta effects including cognitive impairment.
    [Show full text]