DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2011/0003803 A1 Stroman Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) Patent Application Publication (10) Pub. No.: US 2011/0003803 A1 Stroman Et Al US 2011 0003803A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0003803 A1 Stroman et al. (43) Pub. Date: Jan. 6, 2011 (54) COMPOSITIONS AND METHODS FOR Related U.S. Application Data TREATING OPHTHALMIC, OTIC, OR NASAL INFECTIONS (60) Provisional application No. 61/222,625, filed on Jul. 2, 2009. (75) Inventors: David W. Stroman, Irving, TX Publication Classification (US); Masood A. Chowhan, (51) Int. Cl. Arlington, TX (US); Kenneth C. A6II 3/5383 (2006.01) Appell, Burleson, TX (US) C07D 49.8/04 (2006.01) A6IP27/02 (2006.01) Correspondence Address: A6IP27/16 (2006.01) ALCON A6IP3L/00 (2006.01) IP LEGAL, TB4-8, 6201 SOUTH FREEWAY (52) U.S. Cl. ...................................... 514/230.5:544/105 FORTWORTH, TX 76134 (US) (57) ABSTRACT The present invention relates to methods for treating an oph (73) Assignee: ALCON RESEARCH, LTD., Fort thalmic, otic, or nasal infection comprising treating the Worth, TX (US) infected tissue with a composition comprising finafloxacin or a finafloxacin derivative. The present invention also relates to (21) Appl. No.: 12/829,973 antimicrobial compositions comprising finafloxacin or a fina floxacin derivative. The compositions are suitable for the (22) Filed: Jul. 2, 2010 treatment of ophthalmic, otic, or nasal infections. Patent Application Publication Jan. 6, 2011 Sheet 1 of 8 US 2011/0003803 A1 e|'6|- 9 Z 0 ,B.9S #7(O. €5 ZZZZZZZ N. CO LO V of CN V O Patent Application Publication Jan. 6, 2011 Sheet 2 of 8 US 2011/0003803 A1 N Co Ltd v of CN Y O |u/n-O 6o N. CO LO V of CN Y Co Patent Application Publication Jan. 6, 2011 Sheet 3 of 8 US 2011/0003803 A1 S N. CO LO v c Cn Y O ZZZZZZZ N. co Lo V of CN Y Co Patent Application Publication Jan. 6, 2011 Sheet 4 of 8 US 2011/0003803 A1 N 2 SN 2 OO N Co Ltd v c Cn v O. Patent Application Publication Jan. 6, 2011 Sheet 5 of 8 US 2011/0003803 A1 O O OO N Co Ltd v c Cn V Cd (6rd) unouw Patent Application Publication Jan. 6, 2011 Sheet 6 of 8 US 2011/0003803 A1 N 5 CD X O X R O O C .9 O 1. NY sa N O O. O. O. O. O. O O. O. O. C CO CO. Y 3 S. s v (6/6u) uOpeueouOO Patent Application Publication Jan. 6, 2011 Sheet 7 of 8 US 2011/0003803 A1 N 5( s) S. 8H 5. O (u/6u) uole Jueouoo Patent Application Publication Jan. 6, 2011 Sheet 8 of 8 US 2011/0003803 A1 p??eeu?uno 0 US 2011/0003803 A1 Jan. 6, 2011 COMPOSITIONS AND METHODS FOR than half of Pseudomonas strains isolated from otic infections TREATING OPHTHALMIC, OTIC, OR NASAL are quinolone resistant. See Ballenger's Otorhinolaryngol INFECTIONS ogy. Head and Neck Surgery, Snow. J. et al., page 194, (2009). In addition, the external ear is generally an acidic CROSS-REFERENCE TO RELATED environment due to the presence of cerumen. There is accord APPLICATION ingly a need for additional topical compositions for the treat 0001. This application claims priority under 35 U.S.C. ment of otic infection that are efficacious at low pH. S119 to U.S. Provisional Patent Application No. 61/222,625, filed Jul. 2, 2009, the entire contents of which are incorpo BRIEF SUMMARY OF THE INVENTION rated herein by reference. 0008. The present invention relates to compositions for the treatment of ophthalmic, otic, and nasal disorders comprising TECHNICAL FIELD OF THE INVENTION finafloxacin or a pharmaceutically acceptable salt, derivative, 0002 The present invention generally relates to methods enantiomer, or hydrate thereof. In preferred embodiments, for treating an ophthalmic, otic, or nasal disorder. The present Such compositions are for the treatment of ophthalmic, otic, invention specifically relates to treating an ophthalmic, otic, and nasal infections, particularly infections caused by various or nasal infection with a composition comprising finafloxacin bacterial species. Preferred finafloxacin compositions have or a finafloxacin derivative. an acidic pH which provides for increased antimicrobial effi cacy. Additionally, the present invention relates to methods BACKGROUND OF THE INVENTION for treating an infected to ophthalmic, otic, or nasal tissue comprising treating the infected tissue with a composition 0003 Microbial resistance to conventional antimicrobial comprising finafloxacin. treatment is an ongoing concern to medical professionals. 0009. The compositions and methods of the present inven Until the problem of resistance is overcome, a steady Supply tion are useful in the treatment of acute otic infections, par of new treatments and therapies for treating microbial infec ticularly those of the external ear canal Such as acute otitis tions is required in order to blunt the effect of microbe muta externa (AOE) and acute otitis media with tympanostomy tions that render conventional therapies less effective or, in tubes (AOMT). Due to the presence of cerumen, the external certain cases, ineffective. In particular, resistance to qui ear environment is generally of acidic pH. The present inven nolone antibiotics is becoming a concern. tors have unexpectedly found that, when tested at acidic pH, 0004 Quinolone antibiotics are known to have desirable compositions comprising finafloxacin are generally more antimicrobial properties. For example, quinolone compounds efficacious than other quinolone compositions against for use in the treatment of ophthalmic, otic, and nasal condi microbes commonly found in otic infections. Finafloxacin tions are disclosed in U.S. Pat. No. 6,716,830, the entire compositions of the present invention also have low potential contents of which are incorporated by reference herein. for inner ear toxicity when used for the topical treatment of 0005 Finafloxacin has been described as useful in the external ear infections. The compositions and methods of the treatment of H. pylori infections. Buissonniere et al., “Anti present invention are accordingly well Suited for the topical microbial activity of a new fluoroquinolone, finafloxacin, treatment of otic infections. against H. Pylori in comparison to levofloxacin' Helico 0010 Certain finafloxacin compositions provide bacter, Vol. 13(5):465, October 2008; U.S. Pat. No. 6,133, enhanced antimicrobial activity and may be used to treat 260 to Matzke et al. Ophthalmic, otic, and nasal applications infections resulting from quinolone-resistant microbes. Such of finafloxacin are not described. enhanced activity is believed to result from a combination of 0006 To cite one of many applications, the use of compo the increased potency and betterpenetration characteristics of sitions having antimicrobial properties is important for the finafloxacin relative to other antibiotics. Ophthalmic fina treatment of ophthalmic infections such as conjunctivitis. floxacin compositions are particularly well suited for the Conjunctivitis can be caused by various kinds of microbes, topical treatment of ophthalmic infection. Such compositions with most cases being due to bacteria and/or viruses. Unfor can be formulated at a neutral pH and retain their efficacy tunately, conjunctivitis symptoms are not specific to the eti against common ophthalmic pathogens Such as Staphylococ ology of the infectious agent and significant testing may be CS Cai.S. required to determine the causative agent or microbe. Care 0011. The foregoing brief summary broadly describes the must be taken in selecting appropriate agents for treating features and technical advantages of certain embodiments of conjunctivitis, given the sensitive tissues affected by the the present invention. Additional features and technical infection. In view of the above-recited difficulties in treat advantages will be described in the detailed description of the ment, compositions for treating conjunctivitis are needed that invention that follows. Novel features which are believed to have broad-spectrum antimicrobial properties, a benign toxi be characteristic of the invention will be better understood cological profile, and/or characteristics that prevent the trans from the detailed description of the invention when consid mission of contagious infectious agents. ered in connection with any accompanying figures. However, 0007. Otic infections such as acute otitis externa (AOE) figures provided herein are intended to help illustrate the and acute otitis media with tympanostomy tubes (AOMT) are invention or assist with developing an understanding of the preferably treated by topical antimicrobial compositions, as invention, and are not intended to be definitions of the inven the use of oral antimicrobials carries the risk of systemic side tion's scope. effects, and can occasionally fail to eradicate Such infections with the possible development of drug-resistant strains. BRIEF DESCRIPTION OF THE DRAWINGS Recent years have seen a steady increase in quinolone-resis tant strains of Staphylococcus and Pseudomonas bacteria, the 0012. A more complete understanding of the present most common causes of otic infections. In some areas, more invention and the advantages thereof may be acquired by US 2011/0003803 A1 Jan. 6, 2011 referring to the following description, taken in conjunction present invention is also particularly directed to antimicrobial with the figures of the accompanying drawing in which like compositions for and methods of treating ophthalmic, otic, reference numbers indicate like features and wherein: and nasal/sinus infections. 0013 FIGS. 1a-1d are bar charts presenting the results of 0022. Certain embodiments of the present invention are a guinea pig model of otic infection; particularly useful for treating ophthalmic tissue infections. 0014 FIG. 2 is a graph showing comparative corneal per Examples of ophthalmic conditions that may be treated using fusion data for several quinolone antimicrobials; compositions and methods of the present invention include 0015 FIG. 3 presents the results of an ocular pharmaco conjunctivitis, keratitis, blepharitis, dacyrocystitis, kinetic study of finafloxacin and ciprofloxacin in corneal hordeolum and corneal ulcers. The methods and composi tissue following topical administration; tions of the invention may also be used prophylactically in 0016 FIG.
Load more

Recommended publications
  • The Role of Nanobiosensors in Therapeutic Drug Monitoring
    Journal of Personalized Medicine Review Personalized Medicine for Antibiotics: The Role of Nanobiosensors in Therapeutic Drug Monitoring Vivian Garzón 1, Rosa-Helena Bustos 2 and Daniel G. Pinacho 2,* 1 PhD Biosciences Program, Universidad de La Sabana, Chía 140013, Colombia; [email protected] 2 Therapeutical Evidence Group, Clinical Pharmacology, Universidad de La Sabana, Chía 140013, Colombia; [email protected] * Correspondence: [email protected]; Tel.: +57-1-8615555 (ext. 23309) Received: 21 August 2020; Accepted: 7 September 2020; Published: 25 September 2020 Abstract: Due to the high bacterial resistance to antibiotics (AB), it has become necessary to adjust the dose aimed at personalized medicine by means of therapeutic drug monitoring (TDM). TDM is a fundamental tool for measuring the concentration of drugs that have a limited or highly toxic dose in different body fluids, such as blood, plasma, serum, and urine, among others. Using different techniques that allow for the pharmacokinetic (PK) and pharmacodynamic (PD) analysis of the drug, TDM can reduce the risks inherent in treatment. Among these techniques, nanotechnology focused on biosensors, which are relevant due to their versatility, sensitivity, specificity, and low cost. They provide results in real time, using an element for biological recognition coupled to a signal transducer. This review describes recent advances in the quantification of AB using biosensors with a focus on TDM as a fundamental aspect of personalized medicine. Keywords: biosensors; therapeutic drug monitoring (TDM), antibiotic; personalized medicine 1. Introduction The discovery of antibiotics (AB) ushered in a new era of progress in controlling bacterial infections in human health, agriculture, and livestock [1] However, the use of AB has been challenged due to the appearance of multi-resistant bacteria (MDR), which have increased significantly in recent years due to AB mismanagement and have become a global public health problem [2].
    [Show full text]
  • Activity of the Investigational Fluoroquinolone Finafloxacin and Seven Other PD Dr
    Contact information: CORRESPONDING AUTHOR Activity of the Investigational Fluoroquinolone Finafloxacin and Seven Other PD Dr. Reiner Schaumann 49 th ICAAC Institute for Medical Microbiology and Epidemiology of Infectious Diseases San Francisco 2009 Antimicrobial Agents Against 83 Obligately Anaerobic Bacteria. University of Leipzig Liebigstr. 24 1 1 2 1 2 1 D-04103 Leipzig R. SCHAUMANN , G. H. GENZEL , W. STUBBINGS , C. S. STINGU , H. LABISCHINSKI , A. C. RODLOFF Germany E - 1973 Phone +49 341 97 15 200 1Inst. f. Med. Microbiology and Epidemiology of Infectious Diseases, Univ. of Leipzig, Leipzig, Germany; 2MerLion Pharmaceuticals GmbH, Berlin, Germany. Fax +49 341 97 15 209 E-Mail: [email protected] AbstractAbstract MethodsMethods ResultsResults andand DiscussionDiscussion Background: Finafloxacin (FIN) is a novel Bacterial Strains The Figures 2 and 3 show the scatter fluoroquinolone belonging to a 8-cyano subclass 83 obligately anaerobes including reference strains were taken from the histograms of MIC values obtained for FIN culture collection from the Institute for Medical Microbiology and and exhibits enhanced activity at slightly acidic and the seven other antimicrobial agents pH. FIN exhibited superior activity to comparator Epidemiology of Infectious Diseases, University of Leipzig, Germany. The fluoroquinolones in a wide range of rodent strains were collected from clinical specimens at the Institute and from against 83 obligately anaerobic bacteria infection models. With the present study the national and international studies and obtained in part from other included in this study. activity of FIN against 83 recently isolated strains laboratories. The following strains were used: Bacteroides fragils group of obligately anaerobic bacteria including (n=62): B.
    [Show full text]
  • Paper I and II)
    Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1335 Constraints on up-regulation of drug efflux in the evolution of ciprofloxacin resistance LISA PRASKI ALZRIGAT ACTA UNIVERSITATIS UPSALIENSIS ISSN 1651-6206 ISBN 978-91-554-9923-5 UPPSALA urn:nbn:se:uu:diva-320580 2017 Dissertation presented at Uppsala University to be publicly examined in B22, BMC, Husargatan 3, Uppsala, Friday, 9 June 2017 at 09:00 for the degree of Doctor of Philosophy (Faculty of Medicine). The examination will be conducted in English. Faculty examiner: Professor Fernando Baquero (Departamento de Microbiología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain). Abstract Praski Alzrigat, L. 2017. Constraints on up-regulation of drug efflux in the evolution of ciprofloxacin resistance. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1335. 48 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-554-9923-5. The crucial role of antibiotics in modern medicine, in curing infections and enabling advanced medical procedures, is being threatened by the increasing frequency of resistant bacteria. Better understanding of the forces selecting resistance mutations could help develop strategies to optimize the use of antibiotics and slow the spread of resistance. Resistance to ciprofloxacin, a clinically important antibiotic, almost always involves target mutations in DNA gyrase and Topoisomerase IV. Because ciprofloxacin is a substrate of the AcrAB-TolC efflux pump, mutations causing pump up-regulation are also common. Studying the role of efflux pump-regulatory mutations in the development of ciprofloxacin resistance, we found a strong bias against gene-inactivating mutations in marR and acrR in clinical isolates.
    [Show full text]
  • Against Helicobacter Pylori in Vitro and in Vivo Merlion Pharmaceuticals Pte Ltd, Washington DC 2008 05-01 the Capricorn, 1 2 1 1 3 3 1 Science Park 2, A
    Contact information: 48th ICAAC / 46th IDSA, WILL STUBBINGS Antimicrobial Activity of Finafloxacin (FIN) against Helicobacter pylori In Vitro and In Vivo MerLion Pharmaceuticals Pte Ltd, Washington DC 2008 05-01 The Capricorn, 1 2 1 1 3 3 1 Science Park 2, A. BUISSONNIÈRE , H-O. WERLING B. BERGEY , P. LEHOURS , W. STUBBINGS , H. LABISCHINSKI , F. MEGRAUD . Singapore 117528 F1-2038 Phone +65 6829 5600 1INSERM U853, Bordeaux, France, 2Bayer HealthCare AG, Elberfeld, Germany, 3MerLion Pharmaceuticals Pte Ltd, Singapore. [email protected] RevisedRevised abstractabstract MethodsMethods ResultsResults andand DiscussionDiscussion Introduction: FIN is a novel fluoroquinolone (FQ) belonging to a new 8- Minimum inhibitory concentration (MIC) determination Murine model of H. felis infection cyano subclass. FIN exhibits optimal efficacy at slightly acidic pH (5.0 - 6.0), Finafloxacin Levofloxacin Clearance % under which other FQs lose activity. FIN is intended for therapeutic use MICs were determined for FIN and LVX against H. pylori strains (n= 55) that were MIC MIC MIC MIC W 8801, X 7328, 17-8299, H. felis was passaged in mice to achieve a persistent infection that pH 50 90 50 90 X 2752, X 9181, Y 1304 against bacterial infections associated with an acidic environment such as H. obtained from patients gastroscoped in the Southwest of France. MICs were 100 [mg/L] [mg/L] [mg/L] [mg/L] 34-6601 exhibited a similar response to therapy as H. pylori in humans. Triple pylori eradication. The antibacterial activity of FIN, was determined against performed by agar dilution at 3 different pHs: 7.3, 6.3 and 5.3. An inoculum FIN FQ RES and susceptible strains at acidic pH, and against H.
    [Show full text]
  • 200 and 800 Mg) in Healthy Volunteers Receiving a Single Oral Dose
    Pharmacology Chemotherapy 2011;57:97–107 Received: June 9, 2010 DOI: 10.1159/000321028 Accepted after revision: August 30, 2010 Published online: February 28, 2011 Urinary Pharmacokinetics and Bactericidal Activity of Finafloxacin (200 and 800 mg) in Healthy Volunteers Receiving a Single Oral Dose a b d Florian M.E. Wagenlehner Christine M. Wagenlehner Birgit Blenk d e e c Holger Blenk Sabine Schubert Axel Dalhoff Kurt G. Naber a Department of Urology, Pediatric Urology and Andrology, Justus Liebig University Giessen, and b c Department of Anesthesia, Evangelisches Krankenhaus, Giessen , Technical University of Munich, Straubing , d e Department of Microbiology, Nürnberg , and University Hospital Schleswig-Holstein, Campus Kiel, Kiel , Germany Key Words Introduction ؒ Finafloxacin ؒ Urine pharmacokinetics ؒ Pharmacodynamics Urinary bactericidal titers Urinary tract infection (UTI) is one of the most com- mon reasons for medical consultation. Uncomplicated UTI are predominantly caused by Escherichia coli, but Abstract also by Proteus mirabilis and occasionally Klebsiella spp., Background: Finafloxacin is a novel 8-cyano-fluoroquino- other Enterobacteriaceae and Staphylococcus saprophyti- lone under investigation for treatment of urinary tract infec- cus ( ! 5% each) [1–3] . Infections with P. mirabilis are sig- tion. Methods: Urinary concentrations and urinary bacteri- nificantly more common in patients over 50 years, where- cidal titers (UBT) of finafloxacin 200- and 800-mg single dos- as infections with S. saprophyticus are more common in es in 6 healthy volunteers were measured up to 48 h. UBT younger patients. Nosocomial UTI, almost always com- were determined for a reference strain and 9 selected clin- plicated, are caused by a wide range of pathogens, most ical uropathogens at the pH of native, acidified (pH 5.5) frequently E.
    [Show full text]
  • The Grohe Method and Quinolone Antibiotics
    The Grohe method and quinolone antibiotics Antibiotics are medicines that are used to treat bacterial for modern fluoroquinolones. The Grohe process and the infections. They contain active ingredients belonging to var- synthesis of ciprofloxacin sparked Bayer AG’s extensive ious substance classes, with modern fluoroquinolones one research on fluoroquinolones and the global competition of the most important and an indispensable part of both that produced additional potent antibiotics. human and veterinary medicine. It is largely thanks to Klaus Grohe – the “father of Bayer quinolones” – that this entirely In chemical terms, the antibiotics referred to for simplicity synthetic class of antibiotics now plays such a vital role for as quinolones are derived from 1,4-dihydro-4-oxo-3-quin- medical practitioners. From 1965 to 1997, Grohe worked oline carboxylic acid (1) substituted in position 1. as a chemist, carrying out basic research at Bayer AG’s Fluoroquinolones possess a fluorine atom in position 6. In main research laboratory (WHL) in Leverkusen. During this addition, ciprofloxacin (2) has a cyclopropyl group in posi- period, in 1975, he developed the Grohe process – a new tion 1 and also a piperazine group in position 7 (Figure A). multi-stage synthesis method for quinolones. It was this This substituent pattern plays a key role in its excellent achievement that first enabled him to synthesize active an- antibacterial efficacy. tibacterial substances such as ciprofloxacin – the prototype O 5 O 4 3 6 COOH F COOH 7 2 N N N 8 1 H N R (1) (2) Figure A: Basic structure of quinolone (1) (R = various substituents) and ciprofloxacin (2) Quinolones owe their antibacterial efficacy to their inhibition This unique mode of action also makes fluoroquinolones of essential bacterial enzymes – DNA gyrase (topoisomer- highly effective against a large number of pathogenic ase II) and topoisomerase IV.
    [Show full text]
  • 206307Orig1s000
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 206307Orig1s000 OTHER REVIEW(S) NDA 206-307 PMC Development: Product Quality (CMC-Biopharmaceutics) This template should be completed by ONDQA’s Biopharmaceutics or CMC reviewer. For each type of CMC or Biopharmaceutics PMC in the Action Package (See #4 for a list of PMC types). NDA NDA 206-307 Finafloxacin Otic Suspension Product Name: The dissolution method development report with the complete data should be PMC # 1 submitted within 6 months from NDA’s action date. Description: The report should include the following information: a. Solubility and pH data for the drug substance in the proposed dissolution medium; b. Detailed description of the dissolution test being proposed for the evaluation of the proposed drug product and the developmental parameters used to select the proposed dissolution method as the optimal test for the proposed product (i.e., selection of the equipment/ apparatus, in vitro dissolution media, agitation/rotation speed, pH, assay, sink conditions, etc.). The dissolution profile should be complete (i.e., 10, 15, 20, 30, 45, & (b) 60 minutes) and cover at least(4) % of drug release of the label amount or whenever a plateau (i.e., no increase over 3 consecutive time-points) is reached. The use of USP Apparatus 2 with mini-vessels (50-200 ml volume) should be considered for the dissolution testing of this otic suspension drug product. c. Provide the complete dissolution profile data (individual, mean, SD, profiles) for the proposed drug product. The dissolution data should be reported as the cumulative percentage of drug dissolved with time (the percentage is based on the product’s label claim); and d.
    [Show full text]
  • Finafloxacin
    Contains Nonbinding Recommendations Draft Guidance on Finafloxacin This draft guidance, when finalized, will represent the current thinking of the Food and Drug Administration (FDA, or the Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the Office of Generic Drugs. Active Ingredient: Finafloxacin Dosage Form; Route: Suspension/drops; otic Recommended Studies: Two options: in vitro or in vivo study I. In Vitro Option: To qualify for the in vitro option for this drug product, all of the following criteria should be met: 1. The test and Reference Listed Drug (RLD) formulations are qualitatively (Q1)1 and quantitatively (Q2)2 the same. 2. Acceptable comparative physicochemical characterization of the test and Reference Standard (RS) products. The comparative studies should be performed on at least three 3 batches of both the test and RS products and should include: • Polymorphic form of finafloxacin • Crystalline shape and morphology of finafloxacin • Appearance, pH, specific gravity, osmolarity, and viscosity • Soluble fraction of finafloxacin in the final drug product • Drug particle size distribution. The particle size distribution should be compared using PBE (95% upper confidence bound) based on D50 and SPAN [i.e. (D90- D10)/D50)]. The applicant should provide no fewer than ten data sets from three different batches of both the test and reference products for PBE analysis. Full profiles of the particle size distributions should also be submitted for all samples tested.
    [Show full text]
  • Visão De Futuro Para Produção De Antibióticos: Tendências De Pesquisa, Desenvolvimento E Inovação
    UNIVERSIDADE FEDERAL DO RIO DE JANEIRO CRISTINA D’URSO DE SOUZA MENDES SANTOS VISÃO DE FUTURO PARA PRODUÇÃO DE ANTIBIÓTICOS: TENDÊNCIAS DE PESQUISA, DESENVOLVIMENTO E INOVAÇÃO Rio de Janeiro EQ/UFRJ 2014 CRISTINA D ’U RSO DE SOUZA MENDES SANTOS VISÃO DE FUTURO PARA A PRODUÇÃO DE ANTIBIÓTICOS: TENDÊNCIAS DE PESQUISA, DESENVOLVIMENTO E INOVAÇÃO Tese de Doutorado apresentada ao Programa de Pós-Graduação em Tecnologia de Processos Químicos e Bioquímicos, Escola de Química, Universidade Federal do Rio de Janeiro, como requisito parcial à obtenção do título de Doutor em Ciências, D.Sc. Orientadora: Profa. Adelaide Maria de Souza Antunes, D.Sc. Rio de Janeiro 2014 Santos, Cristina d’Urso de Souza Mendes. Visão de futuro para produção de antibióticos: tendências de pesquisa, desenvolvimento e inovação / Cristina d’Urso de Souza Mendes Santos. - Rio de Janeiro, 2014. 216 f.: il.; 29,7 cm. Tese (Doutorado em Ciências) – Universidade Federal do Rio de Janeiro, Escola de Química, Programa de Pós-Graduação em Tecnologia de Processos Químicos e Bioquímicos, Rio de Janeiro, 2014. Orientadora: Adelaide Maria de Souza Antunes. 1. Antibióticos. 2. P&D na Indústria Farmacêutica. 3. Prospecção Tecnológica. 4. Patentes. I. Antunes, Adelaide Maria de Souza. II. Universidade Federal do Rio de Janeiro. Escola de Química. III. Visão de futuro para a produção de antibióticos: tendências de pesquisa, desenvolvimento e inovação. iv v Dedico esta tese à minha mãe querida e amada, que está no céu comemorando esta vitória, que é mais dela do que minha. Dedico também à minha filhinha Malu que sem entender foi a minha maior motivação para concluir esta tese.
    [Show full text]
  • An in Situ High-Throughput Screen Identifies Inhibitors of Intracellular Burkholderia Pseudomallei with Therapeutic Efficacy
    An in situ high-throughput screen identifies inhibitors of intracellular Burkholderia pseudomallei with therapeutic efficacy Philip L. Bulterysa,b,c,1, Isabelle J. Toescac, Michael H. Norrisd,e, Jeffrey P. Maloyc, Sorel T. Fitz-Gibbonf, Bryan Franceg, Babak Toffigg, Marco Morsellif, Nawarat Somprasonge,h, Matteo Pellegrinif,g,i, Herbert P. Schweizere,h, Apichai Tuanyokd,e, Robert Damoiseauxg,j, Christopher T. Frenchc,g,2, and Jeff F. Millerb,c,g,2 aUniversity of California, Los Angeles–California Institute of Technology Medical Scientist Training Program, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; bMolecular Biology Institute, University of California, Los Angeles, CA 90095; cDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095; dDepartment of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611; eEmerging Pathogens Institute, University of Florida, Gainesville, FL 32611; fDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA 90095; gCalifornia NanoSystems Institute, University of California, Los Angeles, CA 90095; hDepartment of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32611; iInstitute of Genomics and Proteomics, University of California, Los Angeles, CA 90095; and jDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095 Contributed by Jeff F. Miller, July 13, 2019 (sent for review April 15, 2019; reviewed by Yunn-Hwen Gan and John J. Mekalanos) Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) are Select Agent pathogens. Concern over malign release against Tier-1 Select Agents that cause melioidosis and glanders, respec- civilian or military targets is heightened in light of their historical tively.
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • A Abacavir Abacavirum Abakaviiri Abagovomab Abagovomabum
    A abacavir abacavirum abakaviiri abagovomab abagovomabum abagovomabi abamectin abamectinum abamektiini abametapir abametapirum abametapiiri abanoquil abanoquilum abanokiili abaperidone abaperidonum abaperidoni abarelix abarelixum abareliksi abatacept abataceptum abatasepti abciximab abciximabum absiksimabi abecarnil abecarnilum abekarniili abediterol abediterolum abediteroli abetimus abetimusum abetimuusi abexinostat abexinostatum abeksinostaatti abicipar pegol abiciparum pegolum abisipaaripegoli abiraterone abirateronum abirateroni abitesartan abitesartanum abitesartaani ablukast ablukastum ablukasti abrilumab abrilumabum abrilumabi abrineurin abrineurinum abrineuriini abunidazol abunidazolum abunidatsoli acadesine acadesinum akadesiini acamprosate acamprosatum akamprosaatti acarbose acarbosum akarboosi acebrochol acebrocholum asebrokoli aceburic acid acidum aceburicum asebuurihappo acebutolol acebutololum asebutololi acecainide acecainidum asekainidi acecarbromal acecarbromalum asekarbromaali aceclidine aceclidinum aseklidiini aceclofenac aceclofenacum aseklofenaakki acedapsone acedapsonum asedapsoni acediasulfone sodium acediasulfonum natricum asediasulfoninatrium acefluranol acefluranolum asefluranoli acefurtiamine acefurtiaminum asefurtiamiini acefylline clofibrol acefyllinum clofibrolum asefylliiniklofibroli acefylline piperazine acefyllinum piperazinum asefylliinipiperatsiini aceglatone aceglatonum aseglatoni aceglutamide aceglutamidum aseglutamidi acemannan acemannanum asemannaani acemetacin acemetacinum asemetasiini aceneuramic
    [Show full text]