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United States Patent (19) 11 Patent Number: 6,066,653 Gregg Et Al
US006066653A United States Patent (19) 11 Patent Number: 6,066,653 Gregg et al. (45) Date of Patent: May 23, 2000 54 METHOD OF TREATING ACID LIPASE FOREIGN PATENT DOCUMENTS DEFICIENCY DISEASES WITH AN MTP 643057A1 3/1995 European Pat. Off.. INHIBITOR AND CHOLESTEROL WO96/26205 8/1996 WIPO. LOWERING DRUGS OTHER PUBLICATIONS 75 Inventors: Richard E. Gregg, Pennington, N.J.; John R. Wetterau, II, Langhorne, Pa. Scriver et all “The Metabolic and Molecular Bases of Inher ited Disease”, Seventh Edition, vol. II, Chapter 82, "Acid 73 Assignee: Bristol-Myers Squibb Co., Princeton, Lipase Deficiency: Wolman Disease and Cholesteryl Ester N.J. Storage Disease”, pp. 2563–2587, (1995). Scriver et all “The Metabolic and Molecular Bases of Inher 21 Appl. No.: 09/005,437 ited Disease”, Seventh Edition, vol. II, Chapter 85, 22 Filed: Jan. 10, 1998 “Niemann-Pick Disease Type C: A Cellular Cholesterol Lipidosis”, pp. 2625–2639, (1995). Related U.S. Application Data 60 Provisional application No. 60/036,183, Jan. 17, 1997. Primary Examiner Kimberly Jordan 51) Int. Cl." ......................... A61K 3.144s. A61k 3/21 Attorney, Agent, or Firm Burton Rodney; Ronald S. 52 U.S. Cl. ........................... s14/325.514,510,514824. "a" 58 Field of Search ..................................... 514/325, 510, 57 ABSTRACT 514/824 A method is provided for inhibiting- - - - - - - or treating diseases 56) References Cited asSociated with acid lipase deficiency by administering to a patient an MTP inhibitor, alone or optionally, in combination U.S. PATENT DOCUMENTS with another cholesterol lowering drug, Such as pravastatin. 4,346,227 8/1982 Terahara et al. ........................ 560/119 5,712,279 1/1998 Biller et al. -
Prevention of Coronary Heart Disease
PREVENTION OF CORONARY PATIENT WITH CHD HEART DISEASE • Obese male patient with previous angina, cardiac catheterization with placement of two stents and now stable. • Notable clinical characteristics: Thomas F . Wh ayne, J r, MD , PhD, FACC Triglycerides 354 mg/dl. Professor of Medicine (Cardiology) HDL 28 mg/dl in men. Gill Heart Institute BP 140/90 mm/Hg. University of Kentucky Fasting glucose 120 mg/dl. November, 2009 • Specific management? Characteristics of Plaques Prone to HIGH SENSENSITIVITY Rupture From Inflammation and LDL CREACTIVE PROTEIN (hs-CRP) Fibrous cap Media • A MARKER OF INFLAMMATION: CRP AND Lumen Lipid hsCRP ARE SAME PROTEIN Core • MAY BE ANOTHER RISK FACTOR AND PLAY A ROLE IN PLAQUE FORMATION “Vulnerable” plaque • MAY PREDICT HIGH RISK ACUTE CORONARY SYNDROME • MAY INDICATE PATIENTS MOST LIKELY TO Lumen RESPOND TO STATINS T lymphocyte Lipid • STATINS SHOWN TO REDUCE CRP Core Macrophage foam cell (tissue factor) “Activated” Intimal SMC (HLA-DR+) – EZETIMIBE ACCENTUATES THIS EFFECT* “Stable” plaque Normal medial SMC • NEED STATIN DOSE RESPONSE CURVE Libby P. Circulation. 1999; 91:284491:2844--2850.2850. *Sager PT, et al. Am J Cardiol. 2003;92:1414-1418. Resultados Estudio VYTAL sobre PCR: Ezetimiba/Simvastatina vs. Atorvastatina en pts con DM II e Hipercolesterolemia (n=1229) CURRENT CLINICALLY USEFUL MARKERS OF INFLAMMATION Atorvastatina E/Simvas Atorvas E/S 10 mg 20 mg 10/20 40 mg 10/40 0 • LIPOPROTEIN-ASSOCIATED Ezetimiba/ --55 Simvastatina PHOSPHOLIPASE A2*. Atorvastatina ® asales --1010 a Sensibilidad – PLAC TEST. t b --1515 --13.713.7 de Al --13.813.8 • HIGH SENSITIVITY C-REACTIVE --2020 # PCR PROTEIN (hsCRP) . -
Nitrate Prodrugs Able to Release Nitric Oxide in a Controlled and Selective
Europäisches Patentamt *EP001336602A1* (19) European Patent Office Office européen des brevets (11) EP 1 336 602 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.7: C07C 205/00, A61K 31/00 20.08.2003 Bulletin 2003/34 (21) Application number: 02425075.5 (22) Date of filing: 13.02.2002 (84) Designated Contracting States: (71) Applicant: Scaramuzzino, Giovanni AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU 20052 Monza (Milano) (IT) MC NL PT SE TR Designated Extension States: (72) Inventor: Scaramuzzino, Giovanni AL LT LV MK RO SI 20052 Monza (Milano) (IT) (54) Nitrate prodrugs able to release nitric oxide in a controlled and selective way and their use for prevention and treatment of inflammatory, ischemic and proliferative diseases (57) New pharmaceutical compounds of general effects and for this reason they are useful for the prep- formula (I): F-(X)q where q is an integer from 1 to 5, pref- aration of medicines for prevention and treatment of in- erably 1; -F is chosen among drugs described in the text, flammatory, ischemic, degenerative and proliferative -X is chosen among 4 groups -M, -T, -V and -Y as de- diseases of musculoskeletal, tegumental, respiratory, scribed in the text. gastrointestinal, genito-urinary and central nervous sys- The compounds of general formula (I) are nitrate tems. prodrugs which can release nitric oxide in vivo in a con- trolled and selective way and without hypotensive side EP 1 336 602 A1 Printed by Jouve, 75001 PARIS (FR) EP 1 336 602 A1 Description [0001] The present invention relates to new nitrate prodrugs which can release nitric oxide in vivo in a controlled and selective way and without the side effects typical of nitrate vasodilators drugs. -
The Evolving Role of Direct Thrombin Inhibitors in Acute Coronary
View metadata, citation and similar papers at core.ac.uk brought to you by CORE Journal of the American College of Cardiology providedVol. by 41, Elsevier No. 4 - SupplPublisher S Connector © 2003 by the American College of Cardiology Foundation ISSN 0735-1097/03/$30.00 Published by Elsevier Science Inc. PII S0735-1097(02)02687-6 The Evolving Role of Direct Thrombin Inhibitors in Acute Coronary Syndromes John Eikelboom, MBBS, MSC, FRACP, FRCPA,* Harvey White, MB, CHB, DSC, FRACP, FACC,† Salim Yusuf, MBBS, DPHIL, FRCP (UK), FRCPC, FACC‡ Perth, Australia; Auckland, New Zealand; and Hamilton, Ontario, Canada The central role of thrombin in the initiation and propagation of intravascular thrombus provides a strong rationale for direct thrombin inhibitors in acute coronary syndromes (ACS). Direct thrombin inhibitors are theoretically likely to be more effective than indirect thrombin inhibitors, such as unfractionated heparin or low-molecular-weight heparin, because the heparins block only circulating thrombin, whereas direct thrombin inhibitors block both circulating and clot-bound thrombin. Several initial phase 3 trials did not demonstrate a convincing benefit of direct thrombin inhibitors over unfractionated heparin. However, the Direct Thrombin Inhibitor Trialists’ Collaboration meta-analysis confirms the superiority of direct thrombin inhibitors, particularly hirudin and bivalirudin, over unfractionated heparin for the prevention of death or myocardial infarction (MI) during treatment in patients with ACS, primarily due to a reduction in MI (odds ratio, 0.80; 95% confidence interval, 0.70 to 0.91) with little impact on death. The absolute risk reduction in the composite of death or MI at the end of treatment (0.8%) was similar at 30 days (0.7%), indicating no loss of benefit after cessation of therapy. -
(12) United States Patent (10) Patent No.: US 8,697,347 B2
USOO8697347B2 (12) UnitedO States Patent (10) Patent No.: US 8,697,347 B2 Sehgal (45) Date of Patent: *Apr. 15, 2014 (54) COMPOSITION FOR PRESERVING OTHER PUBLICATIONS PLATELETS AND METHOD OF USING THE SAME Furman et al., “GPllb-Illa Antagonist-induced Reduction in Platelet Surface Factor ViVa Binding and Phosphatidylserine Expression in (75) Inventor: Lakshman R. Sehgal, Monarch Beach, Whole Blood”. Thromb. Haemost. 84: 492-8 (2000).* CA (US) Uzan, 'Antithrombotic agents'. Chapter 12, Emerging Drugs 3 : 189-208 (1998).* (73) Assignee: Biovec Transfusion, LLC, Chicago, IL Agranenko et al., “Preparing platelet concentrates from banked blood (US) stored for 1-5 days by using tetracycline antibiotics”. Folia Haematologica 110 (6): 879-86 (1982), abstract only.* ( c ) Notice: Subject to any disclaimer, the term of this International Search Report (Application No. PCT/US2003/038.125, patent is extended or adjusted under 35 filed Dec. 2, 2003). U.S.C. 154(b) by 300 days. Abendschein. D.R., et al., “Effects of ZK-807834, a Novel Inhibitor of Factor Xa, on Arterial and Venous Thrombosis in Rabbits', J. This patent is Subject to a terminal dis- Cardiovasc. Pharmacol., vol. 35. No. 5, pp. 796-805, retrieved Oct. claimer. 11, 2006, <http:\\gateway.ut.ovid.com.gwllovidweb.cgi>, May 2000. (21) Appl. No.: 13/098,128 Ostrem, JA, et al., “Discovery of a Novel, Potent, and Specific Family of Factor Xa Inhibitors via Combinatorial Chemistry, Biochemistry, (22) Filed: Apr. 29, 2011 vol. 37, No. 4, pp. 1053-1059, 1998. Hirsh, J. et al., “New antithrombotic agents'. The Lancet, vol. 353, (65) Prior Publication Data pp. -
Properties and Units in Clinical Pharmacology and Toxicology
Pure Appl. Chem., Vol. 72, No. 3, pp. 479–552, 2000. © 2000 IUPAC INTERNATIONAL FEDERATION OF CLINICAL CHEMISTRY AND LABORATORY MEDICINE SCIENTIFIC DIVISION COMMITTEE ON NOMENCLATURE, PROPERTIES, AND UNITS (C-NPU)# and INTERNATIONAL UNION OF PURE AND APPLIED CHEMISTRY CHEMISTRY AND HUMAN HEALTH DIVISION CLINICAL CHEMISTRY SECTION COMMISSION ON NOMENCLATURE, PROPERTIES, AND UNITS (C-NPU)§ PROPERTIES AND UNITS IN THE CLINICAL LABORATORY SCIENCES PART XII. PROPERTIES AND UNITS IN CLINICAL PHARMACOLOGY AND TOXICOLOGY (Technical Report) (IFCC–IUPAC 1999) Prepared for publication by HENRIK OLESEN1, DAVID COWAN2, RAFAEL DE LA TORRE3 , IVAN BRUUNSHUUS1, MORTEN ROHDE1, and DESMOND KENNY4 1Office of Laboratory Informatics, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark; 2Drug Control Centre, London University, King’s College, London, UK; 3IMIM, Dr. Aiguader 80, Barcelona, Spain; 4Dept. of Clinical Biochemistry, Our Lady’s Hospital for Sick Children, Crumlin, Dublin 12, Ireland #§The combined Memberships of the Committee and the Commission (C-NPU) during the preparation of this report (1994–1996) were as follows: Chairman: H. Olesen (Denmark, 1989–1995); D. Kenny (Ireland, 1996); Members: X. Fuentes-Arderiu (Spain, 1991–1997); J. G. Hill (Canada, 1987–1997); D. Kenny (Ireland, 1994–1997); H. Olesen (Denmark, 1985–1995); P. L. Storring (UK, 1989–1995); P. Soares de Araujo (Brazil, 1994–1997); R. Dybkær (Denmark, 1996–1997); C. McDonald (USA, 1996–1997). Please forward comments to: H. Olesen, Office of Laboratory Informatics 76-6-1, Copenhagen University Hospital (Rigshospitalet), 9 Blegdamsvej, DK-2100 Copenhagen, Denmark. E-mail: [email protected] Republication or reproduction of this report or its storage and/or dissemination by electronic means is permitted without the need for formal IUPAC permission on condition that an acknowledgment, with full reference to the source, along with use of the copyright symbol ©, the name IUPAC, and the year of publication, are prominently visible. -
1 CETP Inhibition Improves HDL Function but Leads to Fatty Liver and Insulin Resistance in CETP-Expressing Transgenic Mice on A
Page 1 of 55 Diabetes CETP inhibition improves HDL function but leads to fatty liver and insulin resistance in CETP-expressing transgenic mice on a high-fat diet Lin Zhu1,2, Thao Luu2, Christopher H. Emfinger1,2, Bryan A Parks5, Jeanne Shi2,7, Elijah Trefts3, Fenghua Zeng4, Zsuzsanna Kuklenyik5, Raymond C. Harris4, David H. Wasserman3, Sergio Fazio6 and John M. Stafford1,2,3,* 1VA Tennessee Valley Healthcare System, 2Division of Diabetes, Endocrinology, & Metabolism, 3Department of Molecular Physiology and Biophysics, 4Devision of Nephrology and Hypertension, Vanderbilt University School of Medicine. 5Division of Laboratory Sciences, Centers for Disease Control and Prevention. 6The Center for Preventive Cardiology at the Knight Cardiovascular Institute, Oregon Health & Science University. 7Trinity College of Art and Science, Duke University. * Address correspondence and request for reprints to: John. M. Stafford, 7445D Medical Research Building IV, Nashville, TN 37232-0475, phone (615) 936-6113, fax (615) 936- 1667 Email: [email protected] Running Title: CETP inhibition and insulin resistance Word Count: 5439 Figures: 7 Tables: 1 1 Diabetes Publish Ahead of Print, published online September 13, 2018 Diabetes Page 2 of 55 Abstract In clinical trials inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels but doesn’t robustly improve cardiovascular outcomes. About 2/3 of trial participants were obese. Lower plasma CETP activity is associated with increased cardiovascular risk in human studies, and protective aspects of CETP have been observed in mice fed a high-fat diet (HFD) with regard to metabolic outcomes. To define if CETP inhibition has different effects depending on the presence of obesity, we performed short- term anacetrapib treatment in chow- and HFD-fed CETP-transgenic mice. -
)&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 -
Antithrombotic Treatment After Stroke Due to Intracerebral Haemorrhage (Review)
Cochrane Database of Systematic Reviews Antithrombotic treatment after stroke due to intracerebral haemorrhage (Review) Perry LA, Berge E, Bowditch J, Forfang E, Rønning OM, Hankey GJ, Villanueva E, Al-Shahi Salman R Perry LA, Berge E, Bowditch J, Forfang E, Rønning OM, Hankey GJ, Villanueva E, Al-Shahi Salman R. Antithrombotic treatment after stroke due to intracerebral haemorrhage. Cochrane Database of Systematic Reviews 2017, Issue 5. Art. No.: CD012144. DOI: 10.1002/14651858.CD012144.pub2. www.cochranelibrary.com Antithrombotic treatment after stroke due to intracerebral haemorrhage (Review) Copyright © 2017 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 . ..... 3 BACKGROUND .................................... 5 OBJECTIVES ..................................... 5 METHODS ...................................... 6 RESULTS....................................... 8 Figure1. ..................................... 9 Figure2. ..................................... 11 Figure3. ..................................... 12 DISCUSSION ..................................... 14 AUTHORS’CONCLUSIONS . 15 ACKNOWLEDGEMENTS . 15 REFERENCES ..................................... 15 CHARACTERISTICSOFSTUDIES . 18 DATAANDANALYSES. 31 Analysis 1.2. Comparison 1 Short-term antithrombotic treatment, Outcome 2 Death. 31 Analysis 1.6. Comparison 1 Short-term antithrombotic -
Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017
Q UO N T FA R U T A F E BERMUDA PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 BR 111 / 2017 The Minister responsible for health, in exercise of the power conferred by section 48A(1) of the Pharmacy and Poisons Act 1979, makes the following Order: Citation 1 This Order may be cited as the Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017. Repeals and replaces the Third and Fourth Schedule of the Pharmacy and Poisons Act 1979 2 The Third and Fourth Schedules to the Pharmacy and Poisons Act 1979 are repealed and replaced with— “THIRD SCHEDULE (Sections 25(6); 27(1))) DRUGS OBTAINABLE ONLY ON PRESCRIPTION EXCEPT WHERE SPECIFIED IN THE FOURTH SCHEDULE (PART I AND PART II) Note: The following annotations used in this Schedule have the following meanings: md (maximum dose) i.e. the maximum quantity of the substance contained in the amount of a medicinal product which is recommended to be taken or administered at any one time. 1 PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 mdd (maximum daily dose) i.e. the maximum quantity of the substance that is contained in the amount of a medicinal product which is recommended to be taken or administered in any period of 24 hours. mg milligram ms (maximum strength) i.e. either or, if so specified, both of the following: (a) the maximum quantity of the substance by weight or volume that is contained in the dosage unit of a medicinal product; or (b) the maximum percentage of the substance contained in a medicinal product calculated in terms of w/w, w/v, v/w, or v/v, as appropriate. -
PHARMACEUTICAL APPENDIX to the TARIFF SCHEDULE 2 Table 1
Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 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. -
Title 16. Crimes and Offenses Chapter 13. Controlled Substances Article 1
TITLE 16. CRIMES AND OFFENSES CHAPTER 13. CONTROLLED SUBSTANCES ARTICLE 1. GENERAL PROVISIONS § 16-13-1. Drug related objects (a) As used in this Code section, the term: (1) "Controlled substance" shall have the same meaning as defined in Article 2 of this chapter, relating to controlled substances. For the purposes of this Code section, the term "controlled substance" shall include marijuana as defined by paragraph (16) of Code Section 16-13-21. (2) "Dangerous drug" shall have the same meaning as defined in Article 3 of this chapter, relating to dangerous drugs. (3) "Drug related object" means any machine, instrument, tool, equipment, contrivance, or device which an average person would reasonably conclude is intended to be used for one or more of the following purposes: (A) To introduce into the human body any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (B) To enhance the effect on the human body of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (C) To conceal any quantity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; or (D) To test the strength, effectiveness, or purity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state. (4) "Knowingly" means having general knowledge that a machine, instrument, tool, item of equipment, contrivance, or device is a drug related object or having reasonable grounds to believe that any such object is or may, to an average person, appear to be a drug related object.