DOCSLIB.ORG

WO 2012/145632 Al 26 October 2012 (26.10.2012) P O P C T

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
WO 2012/145632 Al 26 October 2012 (26.10.2012) 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 2012/145632 Al 26 October 2012 (26.10.2012) P O P C T (51) International Patent Classification: (74) Agents: GEORGE, Nikolaos C. et al; Jones Day, 222 A61K 47/00 (2006.01) C08G 63/91 (2006.01) East 41st Street, New York, NY 10017-6702 (US). A61K 47/48 (2006.01) (81) Designated States (unless otherwise indicated, for every (21) International Application Number: kind of national protection available): AE, AG, AL, AM, PCT/US2012/034459 AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (22) International Filing Date: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, 20 April 2012 (20.04.2012) HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, (25) Filing Language: English KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (26) Publication Language: English OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, (30) Priority Data: SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, 61/477,905 2 1 April 201 1 (21.04.201 1) US TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 61/522,901 12 August 201 1 (12.08.201 1) US (84) Designated States (unless otherwise indicated, for every (71) Applicant (for all designated States except US): kind of regional protection available): ARIPO (BW, GH, CERULEAN PHARMA INC. [US/US]; 840 Memorial GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, Drive, 5th Floor, Cambridge, MA 02 139 (US). UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (72) Inventors; and DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, (75) Inventors/Applicants (for US only): FETZER, Oliver, S. LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, [US/US]; 130 Beard Way, Needham, MA 02492 (US). SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, HWANG, Jungyeon [US/US]; 465 Lowell Street, Lexing GW, ML, MR, NE, SN, TD, TG). ton, MA 02420 (US). SOO, Patrick, Lim [CA/US]; 18 Day Street, Apt. 412, Somerville, MA 02144 (US). NG, Published: Pei-Sze [SG/US]; 2 1 Wendell Street, Apt. 17, Cambridge, — with international search report (Art. 21(3)) MA 02138 (US). [DE/US]; 16 Temple SVENSON, Sonke — before the expiration of the time limit for amending the Street, Arlington, MA 02476 (US). YOUNG, Cissy claims and to be republished in the event of receipt of [US/US]; 31 Alben Road, Waban, MA 02468 (US). amendments (Rule 48.2(h)) (54) Title: CYCLODEXTRIN-BASED POLYMERS FOR THERAPEUTIC DELIVERY Particle Size and Strand Number 10 n m 2 ro 3 0 n m Particle Particle Particle r t i e Figure (57) Abstract: Described herein are CDP-therapeutic peptide conjugates, therapeutic delivery systems comprising CDP-therapeutic peptide conjugates, compositions comprising CDP-therapeutic peptide conjugates, dosage forms comprising CDP-therapeutic pep tide conjugates, and kits comprising CDP-therapeutic peptide conjugates. Also disclosed are methods of using (e.g., to treat a dis order) the CDP-therapeutic peptide conjugates, therapeutic delivery systems comprising CDP-therapeutic peptide conjugates, com positions comprising CDP-therapeutic peptide conjugates, dosage forms comprising CDP-therapeutic peptide conjugates, and kits comprising CDP-therapeutic peptide conjugates. CYCLODEXTRIN-BASED POLYMERS FOR THERAPEUTIC DELIVERY This application claims priority to United States Provisional Application No. 61/477,905, filed April 21, 201 1 and United States Provisional Application No. 61/522,901, filed August 12, 201 1, the disclosures of each of which are hereby incorporated by reference in their entireties. BACKGROUND OF INVENTION The delivery of a therapeutic peptide (TP) with controlled release of the therapeutic peptide is desirable to provide optimal use and effectiveness. Controlled release cyclodextrin- based polymer (CDP) systems may increase the efficacy of the therapeutic peptide and minimize problems with patient compliance. SUMMARY OF INVENTION Described herein are CDP-therapeutic peptide conjugates, therapeutic delivery systems comprising CDP-therapeutic peptide conjugates, compositions comprising CDP-therapeutic peptide conjugates, dosage forms comprising CDP-therapeutic peptide conjugates, and kits comprising CDP-therapeutic peptide conjugates. Also disclosed are methods of using (e.g., to treat a disorder) the CDP-therapeutic peptide conjugates, therapeutic delivery systems comprising CDP-therapeutic peptide conjugates, compositions comprising CDP-therapeutic peptide conjugates, dosage forms comprising CDP-therapeutic peptide conjugates, and kits comprising CDP-therapeutic peptide conjugates. For example, the CDP-therapeutic peptide conjugates can be used in the treatment of cancer, inflammatory disorders (e.g., an inflammatory disorder that includes an inflammatory disorder caused by, e.g., an infectious disease), autoimmune disorders, cardiovascular diseases, kidney disease, metabolic disorders, and infectious disease. Also disclosed are methods of making the CDP-therapeutic peptide conjugates. In one aspect, the disclosure features a CDP-therapeutic peptide conjugate. In an embodiment, the CDP-therapeutic peptide conjugate comprises therapeutic peptide molecules coupled, e.g., via a linker such as a linker described herein, to a CDP moiety, e.g., a CDP described herein. In an embodiment, the CDP-therapeutic peptide conjugate comprises a therapeutic peptide coupled via a linker shown herein. In one embodiment, the therapeutic peptide is a peptide described herein. In one embodiment, the CDP is not biodegradable. In one embodiment, the CDP is biodegradable. In one embodiment, the CDP is biocompatible. In one aspect, the disclosure features a method of treating a disorder in a subject in need thereof, comprising administering to the subject a CDP-therapeutic peptide conjugate in an amount effective to treat the disorder. In an embodiment, the CDP-therapeutic peptide conjugate comprises therapeutic peptide molecules coupled, e.g., via a linker such as a linker described herein, to a CDP moiety, e.g., a CDP described herein. In an embodiment, the CDP-therapeutic peptide conjugate comprises a therapeutic peptide coupled via a linker shown herein. In one embodiment, the therapeutic peptide is a peptide described herein. In one embodiment, the CDP is not biodegradable. In one embodiment, the CDP is biodegradable. In one embodiment, the CDP is biocompatible. In one aspect, the disclosure features a method of treating a disorder in a subject in need thereof, comprising administering to the subject a CDP-therapeutic peptide conjugate in an amount effective to treat the disorder, wherein the CDP-therapeutic peptide is of the formula: wherein each L is independently a linker or absent and each D is independently a therapeutic peptide, a prodrug thereof, or absent, and wherein the group has a Mw of 5 kDa or less (e.g., 3.4 kDa) and n is at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, provided that the polymer comprises at least one therapeutic peptide, thereby treating the subject. In one embodiment, the therapeutic peptide is a peptide described herein. In one embodiment, L is independently an amino acid derivative. In one embodiment, the CDP is not biodegradable. In one embodiment, the CDP is biodegradable. In one embodiment, the CDP is biocompatible. In one embodiment, each L of the CDP-therapeutic peptide conjugate is independently an amino acid derivative. In one embodiment, at least a portion of the CDP is covalently attached to the therapeutic peptide through a cysteine moiety. In one embodiment, the linker comprises a moiety formed using "click chemistry" (e.g., as described in WO 2006/1 15547). In one embodiment, the linker comprises an amide bond, an ester bond, a disulfide bond, or a triazole. In one embodiment, the linker comprises a bond that is cleavable under physiological conditions. In one embodiment, the linker is hydrolysable under physiologic conditions or the linker is enzymatically cleavable under physiological conditions (e.g., the linker comprises a disulfide bond which can be reduced under physiological conditions). In one embodiment, the linker is not cleavable under physiological conditions. In one embodiment, at least a portion of the CDP is covalently attached to the therapeutic peptide through the carboxy terminal of the therapeutic peptide. In one embodiment, at least a portion of the CDP is covalently attached to the therapeutic peptide through an amino acid side of the therapeutic peptide. In one embodiment, the therapeutic peptides are from about 1 to about 100 weight % of the conjugate, e.g., from 1 to about 80 weight % of the conjugate, e.g., from 1 to about 70 weight % of the conjugate, e.g., from 1 to about 60 weight % of the conjugate, e.g., from 1 to about 50 weight % of the conjugate, e.g., from 1 to about 40 weight % of the conjugate, e.g., from 1 to about 30 weight % of the conjugate, e.g., from 1 to about 20 weight % of the conjugate, e.g., from 1 to about 10 weight % of the conjugate. In one embodiment, the disorder is cancer, allergies, an inflammatory disease, an auto immune disease, a cardiovascular disease, a renal disease, or a metabolic disorder. In one embodiment, the subject is a human. In one embodiment, the CDP-therapeutic peptide conjugate is administered by intravenous administration. In one embodiment, the CDP-therapeutic peptide conjugate is administered orally. In one aspect, the disclosure features a method of treating a disorder in a subject in need thereof, comprising administering to the subject a CDP-therapeutic peptide conjugate, wherein the CDP-therapeutic peptide conjugate comprises a subunit of the following formula: wherein each L is a therapeutic peptide, a prodrug thereo of 5 kDa or less (e.g., 3.4 kDa) and n is at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, thereby treating the subject.
Load more

Recommended publications
  • Drug Class Review Beta Adrenergic Blockers
    Drug Class Review Beta Adrenergic Blockers Final Report Update 4 July 2009 Update 3: September 2007 Update 2: May 2005 Update 1: September 2004 Original Report: September 2003 The literature on this topic is scanned periodically. The purpose of this report is to make available information regarding the comparative effectiveness and safety profiles of different drugs within pharmaceutical classes. Reports are not usage guidelines, nor should they be read as an endorsement of, or recommendation for, any particular drug, use, or approach. Oregon Health & Science University does not recommend or endorse any guideline or recommendation developed by users of these reports. Mark Helfand, MD, MPH Kim Peterson, MS Vivian Christensen, PhD Tracy Dana, MLS Sujata Thakurta, MPA:HA Drug Effectiveness Review Project Marian McDonagh, PharmD, Principal Investigator Oregon Evidence-based Practice Center Mark Helfand, MD, MPH, Director Oregon Health & Science University Copyright © 2009 by Oregon Health & Science University Portland, Oregon 97239. All rights reserved. Final Report Update 4 Drug Effectiveness Review Project TABLE OF CONTENTS INTRODUCTION .......................................................................................................................... 6 Purpose and Limitations of Evidence Reports........................................................................................ 8 Scope and Key Questions .................................................................................................................... 10 METHODS.................................................................................................................................
    [Show full text]
  • The In¯Uence of Medication on Erectile Function
    International Journal of Impotence Research (1997) 9, 17±26 ß 1997 Stockton Press All rights reserved 0955-9930/97 $12.00 The in¯uence of medication on erectile function W Meinhardt1, RF Kropman2, P Vermeij3, AAB Lycklama aÁ Nijeholt4 and J Zwartendijk4 1Department of Urology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; 2Department of Urology, Leyenburg Hospital, Leyweg 275, 2545 CH The Hague, The Netherlands; 3Pharmacy; and 4Department of Urology, Leiden University Hospital, P.O. Box 9600, 2300 RC Leiden, The Netherlands Keywords: impotence; side-effect; antipsychotic; antihypertensive; physiology; erectile function Introduction stopped their antihypertensive treatment over a ®ve year period, because of side-effects on sexual function.5 In the drug registration procedures sexual Several physiological mechanisms are involved in function is not a major issue. This means that erectile function. A negative in¯uence of prescrip- knowledge of the problem is mainly dependent on tion-drugs on these mechanisms will not always case reports and the lists from side effect registries.6±8 come to the attention of the clinician, whereas a Another way of looking at the problem is drug causing priapism will rarely escape the atten- combining available data on mechanisms of action tion. of drugs with the knowledge of the physiological When erectile function is in¯uenced in a negative mechanisms involved in erectile function. The way compensation may occur. For example, age- advantage of this approach is that remedies may related penile sensory disorders may be compen- evolve from it. sated for by extra stimulation.1 Diminished in¯ux of In this paper we will discuss the subject in the blood will lead to a slower onset of the erection, but following order: may be accepted.
    [Show full text]
  • Pharmacodynamic Evaluation of Β-Blockade Associated with Atenolol
    Pharmacodynamic HYDOXDWLRQRIȕ-blockade associated with atenolol in healthy dogs Mari Waterman Thesis submitted to the faculty of the Virginia Polytechnic Institute and State University in partial fulfillment of the requirements for the degree of Master of Science In Biomedical and Veterinary Sciences Jonathan A. Abbott, Chair Andrea C. Eriksson Jeffrey R. Wilcke July 30, 2018 Blacksburg, VA .H\ZRUGVDWHQROROȕ-blockade, isoproterenol, dog, pharmacodynamic Copyright 2018 Mari Waterman Pharmacodynamic HYDOXDWLRQRIȕ-blockade associated with atenolol in healthy dogs Mari Waterman ABSTRACT Objective: Dosing intervals of 12 and 24 hours for atenolol have been recommended, but an evidentiary basis is lacking. To test the hypothesis that repeated, once-daily oral administration of atenolol attenuates the heart rate response to isoproterenol for 24 hours, we performed a double-blind, randomized, placebo-controlled cross-over experiment. Animals: Twenty healthy dogs Procedures: Dogs were randomly assigned to receive either placebo (P) and then atenolol (A), [1 mg/kg PO q24h] or vice versa. Treatment periods were 5-7 days; time between periods was 7 days. Heart rates (bpm) at rest (HRr DQG GXULQJ FRQVWDQW UDWH > ȝJNJPLQ@ LQIXVLRQ RI isoproterenol (HRi) were electrocardiographically obtained 0, 0.25, 3, 6, 12, 18, and 24 hours after final administration of drug or placebo. A mixed model ANOVA was used to evaluate the effects of treatment (Tr), time after drug or placebo administration (t), interaction of treatment and time (Tr*t) as well as period and sequence on HRr and HRi. Results: Sequence or period effects were not detected. There was a significant effect of Tr (p <0.0001) and Tr*t (p <0.0001) on HRi.
    [Show full text]
  • Norepinephrine Is Required to Promote Wakefulness and for Hypocretin-Induced Arousal in Zebrafish Chanpreet Singh†, Grigorios Oikonomou†, David a Prober*
    RESEARCH ARTICLE elifesciences.org Norepinephrine is required to promote wakefulness and for hypocretin-induced arousal in zebrafish Chanpreet Singh†, Grigorios Oikonomou†, David A Prober* Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States Abstract Pharmacological studies in mammals suggest that norepinephrine (NE) plays an important role in promoting arousal. However, the role of endogenous NE is unclear, with contradicting reports concerning the sleep phenotypes of mice lacking NE due to mutation of dopamine β-hydroxylase (dbh). To investigate NE function in an alternative vertebrate model, we generated dbh mutant zebrafish. In contrast to mice, these animals exhibit dramatically increased sleep. Surprisingly, despite an increase in sleep, dbh mutant zebrafish have a reduced arousal threshold. These phenotypes are also observed in zebrafish treated with small molecules that inhibit NE signaling, suggesting that they are caused by the lack of NE. Using genetic overexpression of hypocretin (Hcrt) and optogenetic activation of hcrt-expressing neurons, we also find that NE is important for Hcrt-induced arousal. These results establish a role for endogenous NE in promoting arousal and indicate that NE is a critical downstream effector of Hcrt neurons. DOI: 10.7554/eLife.07000.001 *For correspondence: dprober@ Introduction caltech.edu Sleep remains among the most persistent and perplexing mysteries in modern biology. Several †These authors contributed studies have shown that neuronal centers that regulate sleep and wakefulness lie predominantly in the equally to this work hypothalamus and brainstem (Pace-Schott and Hobson, 2002; Saper et al., 2005), and many of the neurotransmitters and neuropeptides employed by these centers are known.
    [Show full text]
  • Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set
    MTC eHealth DSI [eHDSI v2.2.2-OR] eHealth DSI – Master Value Set Catalogue Responsible : eHDSI Solution Provider PublishDate : Wed Nov 08 16:16:10 CET 2017 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 1 of 490 MTC Table of Contents epSOSActiveIngredient 4 epSOSAdministrativeGender 148 epSOSAdverseEventType 149 epSOSAllergenNoDrugs 150 epSOSBloodGroup 155 epSOSBloodPressure 156 epSOSCodeNoMedication 157 epSOSCodeProb 158 epSOSConfidentiality 159 epSOSCountry 160 epSOSDisplayLabel 167 epSOSDocumentCode 170 epSOSDoseForm 171 epSOSHealthcareProfessionalRoles 184 epSOSIllnessesandDisorders 186 epSOSLanguage 448 epSOSMedicalDevices 458 epSOSNullFavor 461 epSOSPackage 462 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 2 of 490 MTC epSOSPersonalRelationship 464 epSOSPregnancyInformation 466 epSOSProcedures 467 epSOSReactionAllergy 470 epSOSResolutionOutcome 472 epSOSRoleClass 473 epSOSRouteofAdministration 474 epSOSSections 477 epSOSSeverity 478 epSOSSocialHistory 479 epSOSStatusCode 480 epSOSSubstitutionCode 481 epSOSTelecomAddress 482 epSOSTimingEvent 483 epSOSUnits 484 epSOSUnknownInformation 487 epSOSVaccine 488 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 3 of 490 MTC epSOSActiveIngredient epSOSActiveIngredient Value Set ID 1.3.6.1.4.1.12559.11.10.1.3.1.42.24 TRANSLATIONS Code System ID Code System Version Concept Code Description (FSN) 2.16.840.1.113883.6.73 2017-01 A ALIMENTARY TRACT AND METABOLISM 2.16.840.1.113883.6.73 2017-01
    [Show full text]
  • Pharmaceutical Appendix to the Tariff Schedule 2
    Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2007) (Rev. 2) 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. ABACAVIR 136470-78-5 ACIDUM LIDADRONICUM 63132-38-7 ABAFUNGIN 129639-79-8 ACIDUM SALCAPROZICUM 183990-46-7 ABAMECTIN 65195-55-3 ACIDUM SALCLOBUZICUM 387825-03-8 ABANOQUIL 90402-40-7 ACIFRAN 72420-38-3 ABAPERIDONUM 183849-43-6 ACIPIMOX 51037-30-0 ABARELIX 183552-38-7 ACITAZANOLAST 114607-46-4 ABATACEPTUM 332348-12-6 ACITEMATE 101197-99-3 ABCIXIMAB 143653-53-6 ACITRETIN 55079-83-9 ABECARNIL 111841-85-1 ACIVICIN 42228-92-2 ABETIMUSUM 167362-48-3 ACLANTATE 39633-62-0 ABIRATERONE 154229-19-3 ACLARUBICIN 57576-44-0 ABITESARTAN 137882-98-5 ACLATONIUM NAPADISILATE 55077-30-0 ABLUKAST 96566-25-5 ACODAZOLE 79152-85-5 ABRINEURINUM 178535-93-8 ACOLBIFENUM 182167-02-8 ABUNIDAZOLE 91017-58-2 ACONIAZIDE 13410-86-1 ACADESINE 2627-69-2 ACOTIAMIDUM 185106-16-5 ACAMPROSATE 77337-76-9
    [Show full text]
  • Drugs for Primary Prevention of Atherosclerotic Cardiovascular Disease: an Overview of Systematic Reviews
    Supplementary Online Content Karmali KN, Lloyd-Jones DM, Berendsen MA, et al. Drugs for primary prevention of atherosclerotic cardiovascular disease: an overview of systematic reviews. JAMA Cardiol. Published online April 27, 2016. doi:10.1001/jamacardio.2016.0218. eAppendix 1. Search Documentation Details eAppendix 2. Background, Methods, and Results of Systematic Review of Combination Drug Therapy to Evaluate for Potential Interaction of Effects eAppendix 3. PRISMA Flow Charts for Each Drug Class and Detailed Systematic Review Characteristics and Summary of Included Systematic Reviews and Meta-analyses eAppendix 4. List of Excluded Studies and Reasons for Exclusion This supplementary material has been provided by the authors to give readers additional information about their work. © 2016 American Medical Association. All rights reserved. 1 Downloaded From: https://jamanetwork.com/ on 09/28/2021 eAppendix 1. Search Documentation Details. Database Organizing body Purpose Pros Cons Cochrane Cochrane Library in Database of all available -Curated by the Cochrane -Content is limited to Database of the United Kingdom systematic reviews and Collaboration reviews completed Systematic (UK) protocols published by by the Cochrane Reviews the Cochrane -Only systematic reviews Collaboration Collaboration and systematic review protocols Database of National Health Collection of structured -Curated by Centre for -Only provides Abstracts of Services (NHS) abstracts and Reviews and Dissemination structured abstracts Reviews of Centre for Reviews bibliographic
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]
  • Network-Based Prediction of Drug Combinations
    Corrected: Publisher correction ARTICLE https://doi.org/10.1038/s41467-019-09186-x OPEN Network-based prediction of drug combinations Feixiong Cheng1,2,3,4,5, Istvań A. Kovacś1,2 & Albert-Laszló ́Barabasí1,2,6,7 Drug combinations, offering increased therapeutic efficacy and reduced toxicity, play an important role in treating multiple complex diseases. Yet, our ability to identify and validate effective combinations is limited by a combinatorial explosion, driven by both the large number of drug pairs as well as dosage combinations. Here we propose a network-based methodology to identify clinically efficacious drug combinations for specific diseases. By 1234567890():,; quantifying the network-based relationship between drug targets and disease proteins in the human protein–protein interactome, we show the existence of six distinct classes of drug–drug–disease combinations. Relying on approved drug combinations for hypertension and cancer, we find that only one of the six classes correlates with therapeutic effects: if the targets of the drugs both hit disease module, but target separate neighborhoods. This finding allows us to identify and validate antihypertensive combinations, offering a generic, powerful network methodology to identify efficacious combination therapies in drug development. 1 Center for Complex Networks Research and Department of Physics, Northeastern University, Boston, MA 02115, USA. 2 Center for Cancer Systems Biology and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. 3 Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA. 4 Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA. 5 Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
    [Show full text]
  • Anatomical Classification Guidelines V2020 EPHMRA ANATOMICAL
    EPHMRA ANATOMICAL CLASSIFICATION GUIDELINES 2020 Anatomical Classification Guidelines V2020 "The Anatomical Classification of Pharmaceutical Products has been developed and maintained by the European Pharmaceutical Marketing Research Association (EphMRA) and is therefore the intellectual property of this Association. EphMRA's Classification Committee prepares the guidelines for this classification system and takes care for new entries, changes and improvements in consultation with the product's manufacturer. The contents of the Anatomical Classification of Pharmaceutical Products remain the copyright to EphMRA. Permission for use need not be sought and no fee is required. We would appreciate, however, the acknowledgement of EphMRA Copyright in publications etc. Users of this classification system should keep in mind that Pharmaceutical markets can be segmented according to numerous criteria." © EphMRA 2020 Anatomical Classification Guidelines V2020 CONTENTS PAGE INTRODUCTION A ALIMENTARY TRACT AND METABOLISM 1 B BLOOD AND BLOOD FORMING ORGANS 28 C CARDIOVASCULAR SYSTEM 35 D DERMATOLOGICALS 50 G GENITO-URINARY SYSTEM AND SEX HORMONES 57 H SYSTEMIC HORMONAL PREPARATIONS (EXCLUDING SEX HORMONES) 65 J GENERAL ANTI-INFECTIVES SYSTEMIC 69 K HOSPITAL SOLUTIONS 84 L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS 92 M MUSCULO-SKELETAL SYSTEM 102 N NERVOUS SYSTEM 107 P PARASITOLOGY 118 R RESPIRATORY SYSTEM 120 S SENSORY ORGANS 132 T DIAGNOSTIC AGENTS 139 V VARIOUS 141 Anatomical Classification Guidelines V2020 INTRODUCTION The Anatomical Classification was initiated in 1971 by EphMRA. It has been developed jointly by Intellus/PBIRG and EphMRA. It is a subjective method of grouping certain pharmaceutical products and does not represent any particular market, as would be the case with any other classification system.
    [Show full text]
  • Pharmacological Properties of Beta-Adrenoceptor Blocking Drugs
    Journal of Clinical and Basic Cardiology An Independent International Scientific Journal Journal of Clinical and Basic Cardiology 1998; 1 (1), 5-9 Pharmacological properties of beta-adrenoceptor blocking drugs Borchard U Homepage: www.kup.at/jcbc Online Data Base Search for Authors and Keywords Indexed in Chemical Abstracts EMBASE/Excerpta Medica Krause & Pachernegg GmbH · VERLAG für MEDIZIN und WIRTSCHAFT · A-3003 Gablitz/Austria REVIEWS β-blocking drugs J Clin Bas Cardiol 1998; 1: 5 Pharmacological properties of β-adrenoceptor blocking drugs U. Borchard β-adrenoceptor blocking drugs are widely used for the treat- Pharmacodynamic properties ment of cardiovascular diseases such as arterial hypertension, β β coronary heart disease and supraventricular and ventricular In many organs there is a coexistence of 1- and 2-receptors (Table 1). For example, in the normal human heart about 80% tachyarrhythmias. They may also be beneficial in the hyper- β β β kinetic heart syndrome, hypotensive circulatory disorders, of the -receptors are of the 1-subtype. In heart failure 1- receptors are down-regulated so that a relatively higher pro- portal hypertension, hyperthyroidism, tremour, migraine, β anxiety, psychosomatic disorders or glaucoma. In recent years portion of 2-receptors can be measured [3]. The physiological and therapeutic actions of a β-blocker depend on the actual even patients with heart failure have been successfully treated β β with β-blockers initially given at very low doses. density of 1- and/or 2-receptors in the different organs, on β A great number of β-adrenoceptor blocking drugs are now the affinity of the -blocker and on the local drug concen- available for clinical use which differ widely with respect to tration.
    [Show full text]
  • Medication for Military Aircrew: Current Use, Issues
    RTO-TR-014 AC/323(HFM-014)TP/14 NORTH ATLANTIC TREATY ORGANIZATION RTO-TR-014 RESEARCH AND TECHNOLOGY ORGANIZATION BP 25, 7 RUE ANCELLE, F-92201 NEUILLY-SUR-SEINE CEDEX, FRANCE RTO TECHNICAL REPORT 14 Medication for Military Aircrew: Current Use, Issues, and Strategies for Expanded Options (les M´edicaments pour les equipages´ militaires : Consommation actuelle, questions et strat´egies pour des options elargies)´ Report of the Human Factors and Medicine Panel (HFM) Working Group 26. Published June 2001 Distribution and Availability on Back Cover 7KLVSDJHKDVEHHQGHOLEHUDWHO\OHIWEODQN 3DJHLQWHQWLRQQHOOHPHQWEODQFKH RTO-TR-014 AC/323(HFM-014)TP/14 NORTH ATLANTIC TREATY ORGANIZATION RESEARCH AND TECHNOLOGY ORGANIZATION BP 25, 7 RUE ANCELLE, F-92201 NEUILLY-SUR-SEINE CEDEX, FRANCE RTO TECHNICAL REPORT 14 Medication for Military Aircrew: Current Use, Issues, and Strategies for Expanded Options (les M´edicaments pour les equipages´ militaires : Consommation actuelle, questions et strat´egies pour des options elargies)´ Authors: EDIGER Mark, M.D. (US) Working Group Chairman BENSON, Alan J. (UK), DANESE, Daniele (IT), DAVIDSON, Ronald A., (CA), DOIREAU, Philippe (FR), ELIOPOULOS, Themis (GR), GRAY, Gary W. (CA), LAM, Berry (NL), NICHOLSON, Anthony A., (UK), PARIS, Jean-Fran¸cois, (FR), PICKARD, Jeb S., (US), PIERARD, C. (FR) Co-Authors: GOURBAT, Jean-Pierre (FR), LAGARDE, D. (FR), LALLEMENT G., (FR), PERES, M. (FR), RODIG,¨ E. (GE), STONE, Barbara M. (UK), TURNER, Claire (UK) Report of the Human Factors and Medicine Panel (HFM) Working Group 26. The Research and Technology Organization (RTO) of NATO RTO is the single focus in NATO for Defence Research and Technology activities. Its mission is to conduct and promote cooperative research and information exchange.
    [Show full text]