DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2004/0058896 A1 Dietrich 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 2004/0058896 A1 Dietrich Et Al US 200400.58896A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2004/0058896 A1 Dietrich et al. (43) Pub. Date: Mar. 25, 2004 (54) PHARMACEUTICAL PREPARATION (30) Foreign Application Priority Data COMPRISING AN ACTIVE DISPERSED ON A MATRIX Dec. 7, 2000 (EP)........................................ OO126847.3 (76) Inventors: Rango Dietrich, Konstanz (DE); Publication Classification Rudolf Linder, Kontanz (DE); Hartmut Ney, Konstanz (DE) (51) Int. Cl." ...................... A61K 31156; A61K 31/4439 (52) U.S. Cl. ........................... 514/171; 514/179; 514/338 Correspondence Address: (57) ABSTRACT NATH & ASSOCATES PLLC 1030 FIFTEENTH STREET, N.W. The present invention relates to the field of pharmaceutical SIXTH FLOOR technology and describes a novel advantageous preparation WASHINGTON, DC 20005 (US) for an active ingredient. The novel preparation is Suitable for 9 producing a large number of pharmaceutical dosage forms. (21) Appl. No.: 10/433,398 In the new preparation an active ingredient is present essentially uniformly dispersed in an excipient matrix com (22) PCT Filed: Dec. 6, 2001 posed of one or more excipients Selected from the group of fatty alcohol, triglyceride, partial glyceride and fatty acid (86) PCT No.: PCT/EPO1/14307 eSter. US 2004/0058896 A1 Mar. 25, 2004 PHARMACEUTICAL PREPARATION 0008 Further subject matters are evident from the claims. COMPRISING AN ACTIVE DISPERSED ON A MATRIX 0009. The preparations for the purpose of the invention preferably comprise numerous individual units in which at least one active ingredient particle, preferably a large num TECHNICAL FIELD ber of active ingredient particles, is present in an excipient 0001. The present invention relates to the field of phar matrix composed of the excipients of the invention (also maceutical technology and describes a novel advantageous referred to as active ingredient units hereinafter). The active preparation for an active ingredient. The novel preparation is ingredient is preferably essentially uniformly dispersed, in Suitable for the production of a large number of pharmaceu particular homogeneously dispersed or dissolved, in the tical dosage forms. excipient matrix. A preparation preferably comprises micro Spheres. BACKGROUND ART 0010. The preparations of the invention are distinguished 0002. In order to achieve particular properties of a dosage in particular by high Stability, a release of active ingredient form, Such as, for example, taste masking in the case of which can be controlled by the particle size and composition active ingredients with an unpleasant taste, resistance to of the matrix, good flow characteristics, good compressibil gastric juice in the case of acid-labile active ingredients or ity and by a uniform delivery of active ingredient. In the case controlled release of an active ingredient, normally active of acid-labile active ingredients it is moreover possible to ingredient pellets are provided with an appropriate func achieve, through choice of the matrix excipients, an acid tional coating. If Such coated pellets are then further pro resistance So that it is possible in the case of oral forms to cessed to dosage forms, for example shaped to tablets by dispense with an acid-resistant coating (enteric coating). In compression with excipients, there is a risk that the coating the case of active ingredients which have an unpleasant taste is damaged and thus the functionality is at least partly lost or, for example, Show a local anesthetic effect in the mouth again. after administration, it has been observed that an unpleasant taste of the active ingredient can be masked, and anesthetic DESCRIPTION OF THE INVENTION effects in the mouth can be avoided, by preparations of the invention. It is particularly worthy of mention that the 0003. It is an object of the present invention to provide a preparations of the invention can be further processed to a preparation for active ingredients which is able to retain a large number of pharmaceutical dosage forms without desired functionality and can be further processed to a large thereby losing a given functionality (Such as taste masking, number of pharmaceutical process forms with negligible resistance to gastric juice, slowing of release). Thus, for impairment of a given functionality. example, on compression of the active ingredient units of the invention no or negligible loSS of functionality is observed 0004. It has now been found, surprisingly, that this object even if deformation of the active ingredient units occurs. In is achieved by a preparation in which an active ingredient is contrast to this, with conventional pellets, which normally essentially uniformly dispersed in an excipient matrix com have a functional coating (Such as taste masking, resistance posed of one or more excipients Selected from the group of to gastric juice, slowing of release), a certain degree of fatty alcohol, triglyceride, partial glyceride and fatty acid damage to the coating and thus to the functionality is eSter. observed on further processing to dosage forms, for example 0005 The invention therefore relates to a preparation in on compression to tablets. This may also lead in Some cases which an active ingredient is essentially uniformly dispersed to active ingredient being released in an unwanted way. in an excipient matrix composed of one or more excipients 0011. The particle size of the individual units is advan Selected from the group of fatty alcohol, triglyceride, partial tageously less than or equal to 2 mm, preferably 50-800 uM, glyceride and fatty acid ester. particularly preferably 50-700 um and very particularly 0006. It has further been found that particularly advan preferably 50-600 um. Preference is given to microsphers of tageous preparations can be obtained by adding Solid par a particle size of 50-500 um, particularly preferably of affin to the excipient matrix. The invention therefore relates 50-400 lum. Particular preference is given to monomodal further to a preparation in which an active ingredient is microspheres with a particle size of 50-400 um, particularly essentially uniformly dispersed in an excipient matrix com of 50-200 um. posed of at least one Solid paraffin together with one or more 0012 Active ingredients of the invention are, in particu excipients Selected from the group of fatty alcohol, triglyc lar, active pharmaceutical ingredients. Examples of active eride, partial glyceride and fatty acid ester. ingredients which may form part of the preparations of the 0007. The invention further relates to preparations in invention are, in particular, the active pharmaceutical ingre which an active ingredient is essentially uniformly dispersed dients mentioned below: i) in an excipient matrix composed of a mixture comprising 0013 Adrenergics: at least one fatty alcohol and at least one Solid paraffin, ii) in an excipient matrix comprised of a mixture comprising at 0014 apraclonidine; brimonidine; dapiprazole; least one triglyceride and at least one Solid paraffin, iii) In an deterenol; diplivefrin, dopamine; ephedrine, espro excipient matrix composed of a mixture comprising at least quin; etafedrine, hydroxyamphetamine; levonorde one partial glyceride and at least one Solid paraffin or iv) in frin, metaraminol; norepinephrine; oxidopamine; an excipient matrix composed of a mixture comprising at phenylpropanolamine; prenalterol; propylhexedrine; least one fatty acid ester and at least one Solid paraffin. pseudoephedrine. US 2004/0058896 A1 Mar. 25, 2004 0015 Adrenocorticosteroids: levomethadyl acetate hydrochloride; levonantradol; levorphanol, lofemizole, lofentanil oxalate; lorcina 0016 ciprocinonide; desoxycorticosterone acetate; dol, lomoxicarn; magnesium Salicylate, mefenamic deSoxycorticosterone pivalate; dexamethasone add; menabitan; meperidine, meptaZinol, metha acetate; fludrocortisone acetate; flumoxonide, hydro done; methadyl acetate; methopholine; methotrime cortisone hemisuccinate, methylprednisolone prazine, metkephamid acetate, mimbane, mirfenta hemisuccinate, naflocort, procinonide; timobesone nil; molinaZone; morphine Sulfate; moxazocine; acetate; tipredane. nabitan; nalbuphine, nalmeXOne, namoxyrate; nant 0017 Agents to prevent alcohol abuse: radol, naproxen; naproxen; naproXol; nefopam; neX eridine, noracy methadol; ocfentanil; octaZamide, 0018 disulfiram, acamprosate, milnacipran, fome olvanil; OXetorone; oxycodone; oxycodone; oxyc pizole, lazabemide, nadide, nitrefazole, Sunepitron. odone terephthalate; oxymorphone, pemedolac, pen 0019 Aldosterone antagonists: tamorphone; pentazocine; pentazocine; phenaZopy ridine, phenyramidol; picenadol; pinadoline; 0020 canrenoate; can renone, dicirenone; meXrenoate, prorenoate, Spironolactone, epoStane, pirfenidone, piroXicam olamine, pravadoline; prodi meSpire none; OXprenoate, Spirorenone, SpiroXaSone, lidine, profadol; propiram; propoxyphene, pro prorenone, eplerenone. poxyphene napsilate; proxazole, proXorphan; pyrro liphene, remifentanil; Salcolex, Salethamide maleate; 0021 Amino acids: Salicylamide, Salicylate meglumine; Salsalate, Sali cylate; Spiradoline, Sufentanil; Sufentanil; talmeta 0022 alanine; aspartic acid; cysteine; histidine, iso cin; talniflumate; taloSalate; taZadolene; tebufelone; leucine; leucine; lysine; methionine; phenylalanine; tetrydamine; tifurac, tilidine, tiopinac, tonazocine; proline, Serine; threonine, tryptophan; tyrosine; tramadol; trefentanil; trolamine; Veradoline, Verilo Valine. pam; volazocine, Xorphanol, Xylazine, Zenazocine 0023 Active ingredients
Load more

Recommended publications
  • UC San Francisco Electronic Theses and Dissertations
    UCSF UC San Francisco Electronic Theses and Dissertations Title Machine Learning for Medical Image Analysis and Compound-Target Interactions Permalink https://escholarship.org/uc/item/8c54b5m7 Author Gaskins, Garrett Publication Date 2020 Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California Machine Learning for Medical Image Analysis and Compound-Target Interactions by Garrett Gaskins DISSERTATION Submitted in partial satisfaction of the requirements for degree of DOCTOR OF PHILOSOPHY in Biological and Medical Informatics in the GRADUATE DIVISION of the UNIVERSITY OF CALIFORNIA, SAN FRANCISCO Approved: ______________________________________________________________________________Michael J Keiser Chair ______________________________________________________________________________Jason Gestwicki ______________________________________________________________________________Sourav Bandyopadhyay ______________________________________________________________________________ ______________________________________________________________________________ Committee Members Copyright 2020 by Garrett Gaskins ii ACKNOWLEDGEMENTS The graduate process is quite an experience. There is a subtle difficulty in describing it, as a peculiar quality of its existence is defined by the uniqueness of it all. Everyone I’ve known to be a part of or to have gone through graduate school has described a truly different journey. Perhaps this is integral to what makes the whole thing work. At the least,
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 7,871,995 B2 Bunschoten Et Al
    US00787 1995 B2 (12) United States Patent (10) Patent No.: US 7,871,995 B2 Bunschoten et al. (45) Date of Patent: *Jan. 18, 2011 (54) DRUG DELIVERY SYSTEM COMPRISINGA (52) U.S. Cl. ....................................... 514/171; 514/182 TETRAHYDROXYLATED ESTROGEN FOR (58) Field of Classification Search ................. 514/171, USE IN HORMONAL CONTRACEPTION 514f182 See application file for complete search history. (75) Inventors: Evert Johannes Bunschoten, Heesch (NL); Herman Jan Tijmen Coelingh (56) References Cited Bennink, Driebergen (NL); Christian U.S. PATENT DOCUMENTS Franz Holinka, New York, NY (US) 3,440,320 A 4, 1969 Sackler et al. O O 3,797.494. A 3, 1974 Zaffaroni (73) Assignee: Pantarhei Bioscience B.V., Al Zeist 4,460.372 A 7/1984 Campbell et al. (NL) 4,573.996 A 3/1986 Kwiatek et al. 4,624,665 A 1 1/1986 Nuwayser (*) Notice: Subject to any disclaimer, the term of this 4,722,941 A 2f1988 Eckert et al. patent is extended or adjusted under 35 4,762,717 A 8/1988 Crowley, Jr. U.S.C. 154(b) by 1233 days. 4.937,238 A 6, 1990 Lemon 5,063,507 A 1 1/1991 Lindsey et al. This patent is Subject to a terminal dis- 5,130,137 A 7/1992 Crowley, Jr. claimer. 5,211,952 A 5/1993 Spicer et al. 5,223,261 A 6/1993 Nelson et al. 5,340,584 A 8/1994 Spicer et al. (21) Appl. No.: 10/478,357 5,340,585 A 8/1994 Pike et al. 1-1. 5,340,586 A 8, 1994 Pike et al.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 9,498,481 B2 Rao Et Al
    USOO9498481 B2 (12) United States Patent (10) Patent No.: US 9,498,481 B2 Rao et al. (45) Date of Patent: *Nov. 22, 2016 (54) CYCLOPROPYL MODULATORS OF P2Y12 WO WO95/26325 10, 1995 RECEPTOR WO WO99/O5142 2, 1999 WO WOOO/34283 6, 2000 WO WO O1/92262 12/2001 (71) Applicant: Apharaceuticals. Inc., La WO WO O1/922.63 12/2001 olla, CA (US) WO WO 2011/O17108 2, 2011 (72) Inventors: Tadimeti Rao, San Diego, CA (US); Chengzhi Zhang, San Diego, CA (US) OTHER PUBLICATIONS Drugs of the Future 32(10), 845-853 (2007).* (73) Assignee: Auspex Pharmaceuticals, Inc., LaJolla, Tantry et al. in Expert Opin. Invest. Drugs (2007) 16(2):225-229.* CA (US) Wallentin et al. in the New England Journal of Medicine, 361 (11), 1045-1057 (2009).* (*) Notice: Subject to any disclaimer, the term of this Husted et al. in The European Heart Journal 27, 1038-1047 (2006).* patent is extended or adjusted under 35 Auspex in www.businesswire.com/news/home/20081023005201/ U.S.C. 154(b) by Od en/Auspex-Pharmaceuticals-Announces-Positive-Results-Clinical M YW- (b) by ayS. Study (published: Oct. 23, 2008).* This patent is Subject to a terminal dis- Concert In www.concertpharma. com/news/ claimer ConcertPresentsPreclinicalResultsNAMS.htm (published: Sep. 25. 2008).* Concert2 in Expert Rev. Anti Infect. Ther. 6(6), 782 (2008).* (21) Appl. No.: 14/977,056 Springthorpe et al. in Bioorganic & Medicinal Chemistry Letters 17. 6013-6018 (2007).* (22) Filed: Dec. 21, 2015 Leis et al. in Current Organic Chemistry 2, 131-144 (1998).* Angiolillo et al., Pharmacology of emerging novel platelet inhibi (65) Prior Publication Data tors, American Heart Journal, 2008, 156(2) Supp.
    [Show full text]
  • Health Reports for Mutual Recognition of Medical Prescriptions: State of Play
    The information and views set out in this report are those of the author(s) and do not necessarily reflect the official opinion of the European Union. Neither the European Union institutions and bodies nor any person acting on their behalf may be held responsible for the use which may be made of the information contained therein. Executive Agency for Health and Consumers Health Reports for Mutual Recognition of Medical Prescriptions: State of Play 24 January 2012 Final Report Health Reports for Mutual Recognition of Medical Prescriptions: State of Play Acknowledgements Matrix Insight Ltd would like to thank everyone who has contributed to this research. We are especially grateful to the following institutions for their support throughout the study: the Pharmaceutical Group of the European Union (PGEU) including their national member associations in Denmark, France, Germany, Greece, the Netherlands, Poland and the United Kingdom; the European Medical Association (EMANET); the Observatoire Social Européen (OSE); and The Netherlands Institute for Health Service Research (NIVEL). For questions about the report, please contact Dr Gabriele Birnberg ([email protected] ). Matrix Insight | 24 January 2012 2 Health Reports for Mutual Recognition of Medical Prescriptions: State of Play Executive Summary This study has been carried out in the context of Directive 2011/24/EU of the European Parliament and of the Council of 9 March 2011 on the application of patients’ rights in cross- border healthcare (CBHC). The CBHC Directive stipulates that the European Commission shall adopt measures to facilitate the recognition of prescriptions issued in another Member State (Article 11). At the time of submission of this report, the European Commission was preparing an impact assessment with regards to these measures, designed to help implement Article 11.
    [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]
  • 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.
    [Show full text]
  • Us Anti-Doping Agency
    2019U.S. ANTI-DOPING AGENCY WALLET CARDEXAMPLES OF PROHIBITED AND PERMITTED SUBSTANCES AND METHODS Effective Jan. 1 – Dec. 31, 2019 CATEGORIES OF SUBSTANCES PROHIBITED AT ALL TIMES (IN AND OUT-OF-COMPETITION) • Non-Approved Substances: investigational drugs and pharmaceuticals with no approval by a governmental regulatory health authority for human therapeutic use. • Anabolic Agents: androstenediol, androstenedione, bolasterone, boldenone, clenbuterol, danazol, desoxymethyltestosterone (madol), dehydrochlormethyltestosterone (DHCMT), Prasterone (dehydroepiandrosterone, DHEA , Intrarosa) and its prohormones, drostanolone, epitestosterone, methasterone, methyl-1-testosterone, methyltestosterone (Covaryx, EEMT, Est Estrogens-methyltest DS, Methitest), nandrolone, oxandrolone, prostanozol, Selective Androgen Receptor Modulators (enobosarm, (ostarine, MK-2866), andarine, LGD-4033, RAD-140). stanozolol, testosterone and its metabolites or isomers (Androgel), THG, tibolone, trenbolone, zeranol, zilpaterol, and similar substances. • Beta-2 Agonists: All selective and non-selective beta-2 agonists, including all optical isomers, are prohibited. Most inhaled beta-2 agonists are prohibited, including arformoterol (Brovana), fenoterol, higenamine (norcoclaurine, Tinospora crispa), indacaterol (Arcapta), levalbuterol (Xopenex), metaproternol (Alupent), orciprenaline, olodaterol (Striverdi), pirbuterol (Maxair), terbutaline (Brethaire), vilanterol (Breo). The only exceptions are albuterol, formoterol, and salmeterol by a metered-dose inhaler when used
    [Show full text]
  • Journal of Pharmaceutical and Biomedical Analysis Stability Of
    Journal of Pharmaceutical and Biomedical Analysis 49 (2009) 519–524 Contents lists available at ScienceDirect Journal of Pharmaceutical and Biomedical Analysis journal homepage: www.elsevier.com/locate/jpba Short communication Stability of selected chlorinated thiazide diuretics K. Deventer a,∗, G. Baele b, P. Van Eenoo a, O.J. Pozo a, F.T. Delbeke a a DoCoLab, UGent, Department of Clinical Chemistry, Microbiology and Immunology, Technologiepark 30, B-9052 Zwijnaarde, Belgium b Department of Applied Mathematics and Computer Science, Krijgslaan 281, S9, B-9000 Gent, Belgium article info abstract Article history: In sports, diuretics are used for two main reasons: to flush previously taken prohibited substances with Received 6 August 2008 forced diuresis and in sports where weight classes are involved to achieve acute weight loss. A com- Received in revised form 5 November 2008 mon property observed for thiazides is hydrolysis in aqueous media resulting in the formation of the Accepted 6 November 2008 degradation product aminobenzenedisulphonamide. This degradation product can be observed for sev- Available online 13 November 2008 eral thiazides. Because there is limited information regarding the effect of pH, temperature and light on the stability of thiazides, these parameters were investigated for chlorothiaizide, hydrochlorothiazide Keywords: and altizide. For all three compounds the degradation product could be detected after incubation at pH Doping ◦ Urine 9.5 for 48 h at 60 C. At lower pH and temperature the degradation product could not be detected for all Diuretics compounds. When samples were exposed to UV-light altizide and hydrochlorothiazide were photode- Thiazides graded to chlorothiazide. When the degradation rate between the different compounds was compared Sports for a given temperature and pH, altizide is the most unstable compound.
    [Show full text]
  • The Inhaled Steroid Ciclesonide Blocks SARS-Cov-2 RNA Replication by Targeting Viral
    bioRxiv preprint doi: https://doi.org/10.1101/2020.08.22.258459; this version posted August 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 The inhaled steroid ciclesonide blocks SARS-CoV-2 RNA replication by targeting viral 2 replication-transcription complex in culture cells 3 4 Shutoku Matsuyamaa#, Miyuki Kawasea, Naganori Naoa, Kazuya Shiratoa, Makoto Ujikeb, Wataru 5 Kamitanic, Masayuki Shimojimad, and Shuetsu Fukushid 6 7 aDepartment of Virology III, National Institute of Infectious Diseases, Tokyo, Japan 8 bFaculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Tokyo, Japan 9 cDepartment of Infectious Diseases and Host Defense, Gunma University Graduate School of 10 Medicine, Gunma, Japan 11 dDepartment of Virology I, National Institute of Infectious Diseases, Tokyo, Japan. 12 13 Running Head: Ciclesonide blocks SARS-CoV-2 replication 14 15 #Address correspondence to Shutoku Matsuyama, [email protected] 16 17 Word count: Abstract 149, Text 3,016 bioRxiv preprint doi: https://doi.org/10.1101/2020.08.22.258459; this version posted August 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 18 Abstract 19 We screened steroid compounds to obtain a drug expected to block host inflammatory responses and 20 MERS-CoV replication. Ciclesonide, an inhaled corticosteroid, suppressed replication of MERS-CoV 21 and other coronaviruses, including SARS-CoV-2, the cause of COVID-19, in cultured cells. The 22 effective concentration (EC90) of ciclesonide for SARS-CoV-2 in differentiated human bronchial 23 tracheal epithelial cells was 0.55 μM.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2012/0115729 A1 Qin Et Al
    US 201201.15729A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0115729 A1 Qin et al. (43) Pub. Date: May 10, 2012 (54) PROCESS FOR FORMING FILMS, FIBERS, Publication Classification AND BEADS FROM CHITNOUS BOMASS (51) Int. Cl (75) Inventors: Ying Qin, Tuscaloosa, AL (US); AOIN 25/00 (2006.01) Robin D. Rogers, Tuscaloosa, AL A6II 47/36 (2006.01) AL(US); (US) Daniel T. Daly, Tuscaloosa, tish 9.8 (2006.01)C (52) U.S. Cl. ............ 504/358:536/20: 514/777; 426/658 (73) Assignee: THE BOARD OF TRUSTEES OF THE UNIVERSITY OF 57 ABSTRACT ALABAMA, Tuscaloosa, AL (US) (57) Disclosed is a process for forming films, fibers, and beads (21) Appl. No.: 13/375,245 comprising a chitinous mass, for example, chitin, chitosan obtained from one or more biomasses. The disclosed process (22) PCT Filed: Jun. 1, 2010 can be used to prepare films, fibers, and beads comprising only polymers, i.e., chitin, obtained from a suitable biomass, (86). PCT No.: PCT/US 10/36904 or the films, fibers, and beads can comprise a mixture of polymers obtained from a suitable biomass and a naturally S3712). (4) (c)(1), Date: Jan. 26, 2012 occurring and/or synthetic polymer. Disclosed herein are the (2), (4) Date: an. AO. films, fibers, and beads obtained from the disclosed process. O O This Abstract is presented solely to aid in searching the sub Related U.S. Application Data ject matter disclosed herein and is not intended to define, (60)60) Provisional applicationpp No. 61/182,833,sy- - - s filed on Jun.
    [Show full text]
  • WO 2014/197398 Al 11 December 2014 (11.12.2014) 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 2014/197398 Al 11 December 2014 (11.12.2014) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 9/06 (2006.01) A61K 31/57 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 47/14 (2006.01) A61K 31/573 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K 31/56 (2006.01) A61K 31/58 (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/US20 14/040560 KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, (22) International Filing Date: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 2 June 2014 (02.06.2014) OM, 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, (25) Filing Language: English TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (26) Publication Language: English ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 61/830,53 1 3 June 2013 (03.06.2013) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, (71) Applicant: TOLMAR, INC.
    [Show full text]
  • Attenuated 5-Hydroxytryptamine Receptor-Mediated Responses in Aortae from Streptozotocin-Induced Diabetic Rats G.M
    Br. J. Pharmacol. (1994), 111, 370-376 '." Macmillan Press Ltd, 1994 Attenuated 5-hydroxytryptamine receptor-mediated responses in aortae from streptozotocin-induced diabetic rats G.M. James, 1W.C. Hodgson, E.A. Davis & 2J.M. Haynes Department of Pharmacology, Monash University, Clayton, Victoria, Australia, 3168 1 This study was designed to examine further the attenuated contractile responses to 5-hydroxy- tryptamine (5-HT) previously observed in aortae from diabetic rats. 2 Cumulative concentration-response curves to 5-HT, and the 5-HT receptor agonists, at-methyl 5-HT (a-Me-5-HT, 5-HT21lc agonist), (± )-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 5-HT21IC agonist) and 5-carboxamidotryptamine (5-CT, 5-HTIA/1B/1D agonist), were examined in endothelium- intact and -denuded aortae from 2-week streptozotocin (STZ)-diabetic and control rats. 3 In endothelium-intact and -denuded aortae from diabetic rats, maximum responses to 5-HT and a-Me-5-HT were significantly reduced compared to those of aortae from control rats. Responses to these agonists were inhibited by the 5-HT21lc receptor antagonist, ketanserin (0.1 jAM). 4 The attenuated responses to 5-HT of aortae from diabetic rats were normalized by chronic insulin treatment of the rats (5 units day-', s.c.), but not by altering the glucose concentration of the bathing fluid. 5 The nitric oxide synthase inhibitor N-nitro-L-arginine (NOLA, 0.1 mM) significantly potentiated responses to both 5-HT and a-Me-5-HT in endothelium-intact aortae. However, the difference between maximum responses of aortae from diabetic and control rats was still evident in the presence of NOLA.
    [Show full text]