DOCSLIB.ORG

Method for Stabilizing Arylcarboxylic Acid, Stabilizer Thereof and Aqueous

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Method for Stabilizing Arylcarboxylic Acid, Stabilizer Thereof and Aqueous Europäisches Patentamt *EP001389469B1* (19) European Patent Office Office européen des brevets (11) EP 1 389 469 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.7: A61K 45/06, A61K 31/52, of the grant of the patent: A61K 31/495, A61K 31/60, 26.10.2005 Bulletin 2005/43 A61K 9/00, A61K 47/22 (21) Application number: 03025332.2 // (A61K31/495, 31:19) (22) Date of filing: 03.02.1998 (54) Method for stabilizing arylcarboxylic acid, stabilizer thereof and aqueous solution containing stabilized arylcarboxylic acid Verfahren zum Stabilisieren von Arylcarbonsäuren, dafür verwendbarer Stabilisator und eine stabilisierte Carbonsäure enthaltende wässrige Lösung Méthode pour stabiliser d’acide arylcarboxylique, stabilisateur utilisable pour celle-ci et solution contenant une acide arylcarboxylique stabilisée (84) Designated Contracting States: • PATENT ABSTRACTS OF JAPAN vol. 1997, no. AT BE CH DE DK ES FI FR GB GR IE IT LI LU MC 04, 30 April 1997 (1997-04-30) & JP 08 333246 A NL PT SE (TAISHO PHARMACEUT CO LTD), 17 December 1996 (1996-12-17) (30) Priority: 04.02.1997 JP 2180597 • PATENT ABSTRACTS OF JAPAN vol. 1997, no. 04, 30 April 1997 (1997-04-30) & JP 08 333265 A (43) Date of publication of application: (TAISHO PHARMACEUT CO LTD), 17 December 18.02.2004 Bulletin 2004/08 1996 (1996-12-17) • CHEMICAL ABSTRACTS, vol. 122, no. 26, 26 (62) Document number(s) of the earlier application(s) in June 1995 (1995-06-26) Columbus, Ohio, US; accordance with Art. 76 EPC: abstract no. 322527, VAN WIE BERGAMINI ET 98101804.7 / 0 856 310 AL.: "OPHTHALMIC FORMULATION BASED ON A STEROIDAL OR NONSTEROIDAL (73) Proprietor: Senju Pharmaceutical Co., Ltd. ANTIINFLAMMATORY AGENT AND A DNA Osaka-shi, Osaka 541-0046 (JP) GYRASE-INHIBITING ANTIBIOTIC" XP002123861 & ES 2 065 846 A (LABORATORIOS (72) Inventor: Shirou, Sawa CUSI, S.A.) 16 February 1995 (1995-02-16) Kobe-shi Hyogo 651-2116 (JP) • PATENT ABSTRACTS OF JAPAN vol. 1997, no. 10, 31 October 1997 (1997-10-31) & JP 09 157162 (74) Representative: von Kreisler, Alek et al A (SATO SEIYAKU KK;R P SHIILA- KK), 17 June Patentanwälte, 1997 (1997-06-17) von Kreisler-Selting-Werner, • PATENT ABSTRACTS OF JAPAN vol. 1995, no. Bahnhofsvorplatz 1 (Deichmannhaus) 07, 31 August 1995 (1995-08-31) & JP 07 097325 50667 Köln (DE) A (TAKEDA CHEM IND LTD), 11 April 1995 (1995-04-11) (56) References cited: EP-A- 0 105 635 EP-A- 0 269 278 EP-A- 0 359 195 EP-A- 0 621 036 EP-A- 0 631 782 WO-A-93/17716 WO-A-95/07082 WO-A-96/29997 WO-A-97/49405 CA-A- 1 336 687 GB-A- 873 526 GB-A- 2 082 456 US-A- 4 794 117 Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 1 389 469 B1 Printed by Jouve, 75001 PARIS (FR) EP 1 389 469 B1 Description [0001] The present invention relates to a method for stabilizing arylcarboxylic acid, which is an acidic compound and which has an antiinflammatory activity, or a pharmacologically acceptable salt thereof. 5 BACKGROUND OF THE INVENTION [0002] Arylcarboxylic acid and pharmacologically acceptable salts thereof have been known to be extremely superior antiinflammatory agents. However, said arylcarboxylic acids, particularly pranoprofen, diclofenac and bromfenac, are 10 associated with a problem that they become unstable in an aqueous solution. [0003] Arylcarboxylic acid and pharmacologically acceptable salts thereof have been also known to be stabilized by adding an antioxidant, by adjusting the pH, concentration and ionic strength thereof, by shutting out the light, and the like. These methods, nevertheless, cannot provide sufficient stability at lower temperatures. [0004] Thus, an aqueous solution has not been provided which contains an arylcarboxylic acid or a pharmacologically 15 acceptable salt thereof, particularly pranoprofen, dicrofenac or bromfenac, and which has sufficient stability at lower temperatures. [0005] While WO9632941 A1 discloses pranoprofen combined with an organic amine, it does not disclose the het- erocyclic base to be used in the present invention. [0006] JP 08333246 (PATENT ABSTRACTS OF JAPAN vol 1997, no. 04) discloses a method for stabilizing an aryl- 20 carboxylic acid, which comprises adding a purine base. SUMMARY OF THE INVENTION [0007] It is therefore an object of the present invention to provide a method for stabilizing an arylcarboxylic acid and 25 a pharmacologically acceptable salt thereof. [0008] According to the present invention, it has now been found that the addition of a pyridonecarboxylic acid to an arylcarboxylic acid or a pharmacologically acceptable salt thereof leads to successful stabilization thereof, particularly pranoprofen, at every temperature range, particularly at low temperatures. [0009] Thus, the present invention provides the following. 30 [0010] A method for stabilizing an arylcarboxylic acid or a pharmacologically acceptable salt thereof in an aqueous solution, which comprises adding (a) a pyridonecarboxylic acid of the formula (IV): 35 40 45 wherein. X is a carbon atom or a nitrogen atom; and R12, R13, R14 and R15 are the same or different and each is a hydrogen atom; a halogen; a carboxyl group, an optionally substituted C1-C6 alkyl group; an optionally substituted C3-C9 cycloalkyl group; 50 an acyl group selected from the group consisting of formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, benzoyl, naphthoyl, toluoyl and salicyloyl, which may be substituted by C1-C3 alkyl, C1-C3 alkoxy, C1-C2 alkylthio, C1-C3 alkylamino, cyclo(C3-C6)alkyl, cyclo (C3-C6)alkenyl, halogen, amino, amino protecting group, hydroxy, protected hydroxy cy- ano, nitro, carboxy, protected carboxy, sulfo, sulfamoyl, imino, oxo, amino(C1-C2)alkyl, 55 carbamoyloxy or hydroxy(C1-C3)alkyl; an optionally substituted aryl group or an option- ally substituted heterocyclic group; wherein R12 and R13 optionally form a 4- to 6-membered heterocyclic group with the adjacent nitrogen atom 2 EP 1 389 469 B1 and X, and R14 and R15 optionally form a 4- to 6-membered heterocyclic group with the adjacent carbon atom, provided that when X is a nitrogen atom, R13 is void, or (b) cinoxacin or sparfloxacin, 5 or a pharmacologically acceptable salt thereof, to an arylearboxylic acid of the formula (I) 1 1 L -R COOH (I) 10 wherein L1 is an optionally substituted heterocyclic group or aryl group having not more than 14 carbon atoms; and R1 is an optionally substituted alkyl group having not more than 4 carbon atoms or a single bond, 15 or a pharmacologically acceptable salt thereof. DETAILED DESCRIPTION OF THE INVENTION 20 [0011] The stabilizing method of the present invention comprises the addition of a stabilizer containing a pyridone- carboxylic acid as an active ingredient to an arylcarboxylic acid, which is an acidic compound and which has an anti- inflammatory activity, or a pharmacologically acceptable salt thereof. For example, a pyridonecarboxylic acid is added to an arylcarboxylic acid or a pharmacologically acceptable salt thereof. [0012] To be specific, an arylcarboxylic acid and a pyridonecarboxylic acid are dissolved in water and the pH thereof 25 is adjusted with boric acid, acetic acid, phosphoric acid, which is followed by lyophilization where necessary. [0013] While the pH varies depending on the kind of arylcarboxylic acid, it is generally 5-9, preferably about 6-8. [0014] Said pyridonecarboxylic acid may be any as long as it has the formula (IV) as defined above. [0015] The alkyl of the "optionally substituted C1-C6 alkyl group" may be a linear or branched one, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, isohexyl, and neohexyl. 30 [0016] The cycloalkyl of the "optionally substituted C3-C9 cycloalkyl group" is exemplified by cyclopropyl, cyclobutyl, cyalopentyl, cyclohexyl, and cycloheptyl. [0017] The substituents of the above-mentioned C1-C6 alkyl group and C3-C9 cycloalkyl group include C1-C3 alkyl group, and halogen. [0018] The lower acyl of the "optionally substituted lower acyl group" may be, for example, formyl group, acetyl group, 35 propionyl group, butyryl group, isobutyryl group, valeryl group, benzoyl group, naphthoyl group, toluoyl group, and salicyloyl group. [0019] The above-mentioned acyl may be substituted by suitable substituents which may be the same or different, such as lower alkyl (e.g., methyl, ethyl, propyl); 40 lower alkoxy (e.g., methoxy, ethoxy, propoxy); lower alkylthio (e.g., methylthio, ethylthio); lower alkylamino (e.g., methylamino, ethylamino, and propylamino); cyclo(lower)alkyl such as cyclo(C3-C6)alkyl (e.g., cyclopentyl, and cyclohexyl); cyclo(lower)alkenyl such as cyclo(C3-C6)alkenyl (e.g., cycloxenyl, and cyclohexadienyl); 45 halogen (e.g., fluorine, chlorine, bromine and iodine); amino; amino protecting group; hydroxy; protected hydroxy; cyano; nitro; carboxy; protected carboxy; sulfo; sulfamoyl; imino; oxo; amino(lower)alkyl (e.g., aminomethyl, aminoethyl), carbamoyloxy, hydroxy(lower)alkyl (e.g., hydroxymethyl, 1- or 2-hy- droxyethyl, 1- or 2- or 3-hydroxypropyl). 50 [0020] The aryl of the "optionally substituted aryl group" is exemplified by phenyl, and naphthyl, with preference given to naphthyl. [0021] The heterocyclic group of the optionally substituted heterocyclic group
Load more

Recommended publications
  • What Are the Acute Treatments for Migraine and How Are They Used?
    2. Acute Treatment CQ II-2-1 What are the acute treatments for migraine and how are they used? Recommendation The mainstay of acute treatment for migraine is pharmacotherapy. The drugs used include (1) acetaminophen, (2) non-steroidal anti-inflammatory drugs (NSAIDs), (3) ergotamines, (4) triptans and (5) antiemetics. Stratified treatment according to the severity of migraine is recommended: use NSAIDs such as aspirin and naproxen for mild to moderate headache, and use triptans for moderate to severe headache, or even mild to moderate headache when NSAIDs were ineffective in the past. It is necessary to give guidance and cautions to patients having acute attacks, and explain the methods of using medications (timing, dose, frequency of use) and medication use during pregnancy and breast-feeding. Grade A Background and Objective The objective of acute treatment is to resolve the migraine attack completely and rapidly and restore the patient’s normal functions. An ideal treatment should have the following characteristics: (1) resolves pain and associated symptoms rapidly; (2) is consistently effective; (3) no recurrence; (4) no need for additional use of medication; (5) no adverse effects; (6) can be administered by the patients themselves; and (7) low cost. Literature was searched to identify acute treatments that satisfy the above conditions. Comments and Evidence The acute treatment drugs for migraine generally include (1) acetaminophens, (2) non-steroidal anti-inflammatory drugs (NSAIDs), (3) ergotamines, (4) triptans, and (5) antiemetics. For severe migraines including status migrainosus and migraine attacks refractory to treatment, (6) anesthetics, and (7) corticosteroids (dexamethasone) are used (Tables 1 and 2).1)-9) There are two approaches to the selection and sequencing of these medications: “step care” and “stratified care”.
    [Show full text]
  • Horsemen's Information 2016和文TGP 1 薬物修正後 E
    [Conditions] 1 Date December 29 (Tue), 2020 2020 Oi Racetrack, Race 10 2 Location TCK, Oi Racetrack 3 Race The 66th Running of Tokyo Daishoten (GI) 4 Eligibility Thoroughbreds, 3 years old & up 5 Full Gate 16 horses 6 Foreign Runners Selected by the selection committee from among the pre-entered horses. 7 Distance 2,000m, 1 1/4 mile (Right-handed, dirt course) 8 Weight 3 years old: 121.5 lbs,4 years old & up: 125.5 lbs, Female: 4.4 lbs less For 3 year-old-horses from the southern hemisphere, reduce 4.4 lbs from the above weight. 9 Purse Unit: 1,000 JPY Prize Purse & Bonus money Running Record 1st place 6th place allowances prize *1 prize *2 1st place 2nd place 3rd place 4th place 5th place or lower Owner 80,000 28,000 16,000 8,000 4,000 300 300 50 1,600 Trainer 880 70 60 50 40 30 30 80 Jockey 120 110 100 80 70 60 30 80 Groom 80 70 60 50 40 30 30 80 Rider 30 30 80 *1 Paid for the runner who broke the previous record and also set the best record during the race. *2 Prize equivalent to the amount listed in the table above is presented. *3 1 USD= 105.88 JPY (As of August,2020) 10 Handling of Late Scratch No allowance is paid in the case of a late scratch (including cancelation of race due to standstill in a starting gate) approved by TCK, Stewards, and Starter. However, if the chairman of the race meeting operation committee deems that the horse is involved in an accident not caused by the horse, the owner is given an running allowance.
    [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]
  • The Involvement of Endoplasmic Reticulum Stress in the Suppression of Colorectal Tumorigenesis by Tolfenamic Acid
    Published OnlineFirst October 8, 2013; DOI: 10.1158/1940-6207.CAPR-13-0220 Cancer Prevention Research Article Research The Involvement of Endoplasmic Reticulum Stress in the Suppression of Colorectal Tumorigenesis by Tolfenamic Acid Xiaobo Zhang1,2, Seong-Ho Lee3, Kyung-Won Min2, Michael F. McEntee2, Jin Boo Jeong3, Qingwang Li1, and Seung Joon Baek2 Abstract The nonsteroidal anti-inflammatory drug tolfenamic acid has been shown to suppress cancer cell growth and tumorigenesis in different cancer models. However, the underlying mechanism by which tolfenamic acid exerts its antitumorigenic effect remains unclear. Previous data from our group and others indicate that tolfenamic acid alters expression of apoptosis- and cell-cycle arrest–related genes in colorectal cancer cells. þ Here, we show that tolfenamic acid markedly reduced the number of polyps and tumor load in APCmin/ mice, accompanied with cyclin D1 downregulation in vitro and in vivo. Mechanistically, tolfenamic acid promotes endoplasmic reticulum (ER) stress, resulting in activation of the unfolded protein response (UPR) signaling pathway, of which PERK-mediated phosphorylation of eukaryotic translation initiation factor 2a (eIF2a) induces the repression of cyclin D1 translation. Moreover, the PERK-eIF2a-ATF4 branch of the UPR pathway plays a role in tolfenamic acid-induced apoptosis in colorectal cancer cells, as silencing ATF4 attenuates tolfenamic acid-induced apoptosis. Taken together, these results suggest ER stress is involved in tolfenamic acid-induced inhibition of colorectal cancer cell growth, which could contribute to antitumor- igenesis in a mouse model. Cancer Prev Res; 6(12); 1–11. Ó2013 AACR. Introduction and has received much attention since the inhibition of Colorectal cancer is the third-leading cause of cancer- COX-2 activity produces adverse effects (5).
    [Show full text]
  • 4 Supplementary File
    Supplemental Material for High-throughput screening discovers anti-fibrotic properties of Haloperidol by hindering myofibroblast activation Michael Rehman1, Simone Vodret1, Luca Braga2, Corrado Guarnaccia3, Fulvio Celsi4, Giulia Rossetti5, Valentina Martinelli2, Tiziana Battini1, Carlin Long2, Kristina Vukusic1, Tea Kocijan1, Chiara Collesi2,6, Nadja Ring1, Natasa Skoko3, Mauro Giacca2,6, Giannino Del Sal7,8, Marco Confalonieri6, Marcello Raspa9, Alessandro Marcello10, Michael P. Myers11, Sergio Crovella3, Paolo Carloni5, Serena Zacchigna1,6 1Cardiovascular Biology, 2Molecular Medicine, 3Biotechnology Development, 10Molecular Virology, and 11Protein Networks Laboratories, International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano, 34149, Trieste, Italy 4Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy 5Computational Biomedicine Section, Institute of Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich GmbH, 52425, Jülich, Germany 6Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy 7National Laboratory CIB, Area Science Park Padriciano, Trieste, 34149, Italy 8Department of Life Sciences, University of Trieste, Trieste, 34127, Italy 9Consiglio Nazionale delle Ricerche (IBCN), CNR-Campus International Development (EMMA- INFRAFRONTIER-IMPC), Rome, Italy This PDF file includes: Supplementary Methods Supplementary References Supplementary Figures with legends 1 – 18 Supplementary Tables with legends 1 – 5 Supplementary Movie legends 1, 2 Supplementary Methods Cell culture Primary murine fibroblasts were isolated from skin, lung, kidney and hearts of adult CD1, C57BL/6 or aSMA-RFP/COLL-EGFP mice (1) by mechanical and enzymatic tissue digestion. Briefly, tissue was chopped in small chunks that were digested using a mixture of enzymes (Miltenyi Biotec, 130- 098-305) for 1 hour at 37°C with mechanical dissociation followed by filtration through a 70 µm cell strainer and centrifugation.
    [Show full text]
  • Antioxidant and Anti-Inflammatory Agents Mitigate Pathology in A
    Human Molecular Genetics, 2015, Vol. 24, No. 14 3918–3928 doi: 10.1093/hmg/ddv122 Advance Access Publication Date: 9 April 2015 Original Article ORIGINAL ARTICLE Antioxidant and anti-inflammatory agents mitigate pathology in a mouse model of pseudoachondroplasia Karen L. Posey1,*, Francoise Coustry1, Alka C. Veerisetty1, Downloaded from Mohammad Hossain1, Joseph L. Alcorn1 and Jacqueline T. Hecht1,2 1Department of Pediatrics, University of Texas Medical School at Houston, Houston, TX, USA and 2Shriners Hospital for Children, Houston, TX, USA http://hmg.oxfordjournals.org/ *To whom correspondence should be addressed. Tel: +1 7135005786; Fax: +1 7135005689; Email: [email protected] Abstract Pseudoachondroplasia (PSACH), a severe short-limb dwarfing condition, results from mutations that cause misfolding of the cartilage oligomeric matrix protein (COMP). Accumulated COMP in growth plate chondrocytes activates endoplasmic reticulum stress, leading to inflammation and chondrocyte death. Using a MT-COMP mouse model of PSACH that recapitulates the molecular and clinical PSACH phenotype, we previously reported that oxidative stress and inflammation play important and at HAM-TMC Library on October 13, 2015 unappreciated roles in PSACH pathology. In this study, we assessed the ability of antioxidant and anti-inflammatory agents to affect skeletal and cellular pathology in our mouse model of PSACH. Treatment of MT-COMP mice with aspirin or resveratrol from birth to P28 decreased mutant COMP intracellular retention and chondrocyte cell death, and restored chondrocyte proliferation. Inflammatory markers associated with cartilage degradation and eosinophils were present in the joints of untreated juvenile MT-COMP mice, but were undetectable in treated mice. Most importantly, these treatments resulted in significantly increased femur length.
    [Show full text]
  • S1 Table. List of Medications Analyzed in Present Study Drug
    S1 Table. List of medications analyzed in present study Drug class Drugs Propofol, ketamine, etomidate, Barbiturate (1) (thiopental) Benzodiazepines (28) (midazolam, lorazepam, clonazepam, diazepam, chlordiazepoxide, oxazepam, potassium Sedatives clorazepate, bromazepam, clobazam, alprazolam, pinazepam, (32 drugs) nordazepam, fludiazepam, ethyl loflazepate, etizolam, clotiazepam, tofisopam, flurazepam, flunitrazepam, estazolam, triazolam, lormetazepam, temazepam, brotizolam, quazepam, loprazolam, zopiclone, zolpidem) Fentanyl, alfentanil, sufentanil, remifentanil, morphine, Opioid analgesics hydromorphone, nicomorphine, oxycodone, tramadol, (10 drugs) pethidine Acetaminophen, Non-steroidal anti-inflammatory drugs (36) (celecoxib, polmacoxib, etoricoxib, nimesulide, aceclofenac, acemetacin, amfenac, cinnoxicam, dexibuprofen, diclofenac, emorfazone, Non-opioid analgesics etodolac, fenoprofen, flufenamic acid, flurbiprofen, ibuprofen, (44 drugs) ketoprofen, ketorolac, lornoxicam, loxoprofen, mefenamiate, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, pranoprofen, proglumetacin, sulindac, talniflumate, tenoxicam, tiaprofenic acid, zaltoprofen, morniflumate, pelubiprofen, indomethacin), Anticonvulsants (7) (gabapentin, pregabalin, lamotrigine, levetiracetam, carbamazepine, valproic acid, lacosamide) Vecuronium, rocuronium bromide, cisatracurium, atracurium, Neuromuscular hexafluronium, pipecuronium bromide, doxacurium chloride, blocking agents fazadinium bromide, mivacurium chloride, (12 drugs) pancuronium, gallamine, succinylcholine
    [Show full text]
  • In Silico Prediction of Interactions Between Site II on Human Serum Albumin and Profen Drugs
    Hindawi Publishing Corporation ISRN Pharmaceutics Volume 2013, Article ID 818364, 8 pages http://dx.doi.org/10.1155/2013/818364 Research Article In Silico Prediction of Interactions between Site II on Human Serum Albumin and Profen Drugs Hideto Isogai and Noriaki Hirayama Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan Correspondence should be addressed to Noriaki Hirayama; [email protected] Received 21 January 2013; Accepted 6 February 2013 Academic Editors: R. A. Caceres, A. Ghosal, and H. Sah Copyright © 2013 H. Isogai and N. Hirayama. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Since binding of a drug molecule to human serum albumin (HSA) significantly affects the pharmacokinetics of the drug, it is highly desirable to predict the binding affinity of the drug. Profen drugs are a widely used class of nonsteroidal anti-inflammatory drugs and it has been reported that several members of the profen class specifically bind to one of the main binding sites named site II. The actual binding mode of only ibuprofen has been directly confirmed by X-ray crystallography. Therefore, it is of interest whether other profen drugs are site II binders. Docking simulations using multiple template structures of HSA from three crystal structures of complexes between drugs and HSA have demonstrated that most of the currently available profen drugs should be site II binders. 1. Introduction center. Based on the reliable crystal structures, structure- based approaches are possible.
    [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]
  • Prophylactic Non-Steroidal Anti-Inflammatory Drugs for the Prevention of Macular Oedema After Cataract Surgery (Review)
    Cochrane Database of Systematic Reviews Prophylactic non-steroidal anti-inflammatory drugs for the prevention of macular oedema after cataract surgery (Review) Lim BX, Lim CHL, Lim DK, Evans JR, Bunce C, Wormald R Lim BX, Lim CHL, Lim DK, Evans JR, Bunce C, Wormald R. Prophylactic non-steroidal anti-inflammatory drugs for the prevention of macular oedema after cataract surgery. Cochrane Database of Systematic Reviews 2016, Issue 11. Art. No.: CD006683. DOI: 10.1002/14651858.CD006683.pub3. www.cochranelibrary.com Prophylactic non-steroidal anti-inflammatory drugs for the prevention of macular oedema after cataract surgery (Review) Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . ..... 4 BACKGROUND .................................... 7 OBJECTIVES ..................................... 8 METHODS ...................................... 8 RESULTS....................................... 11 Figure1. ..................................... 12 Figure2. ..................................... 15 Figure3. ..................................... 18 Figure4. ..................................... 20 ADDITIONALSUMMARYOFFINDINGS . 20 DISCUSSION ..................................... 23 AUTHORS’CONCLUSIONS . 24 ACKNOWLEDGEMENTS . 24 REFERENCES ..................................... 25 CHARACTERISTICSOFSTUDIES . 30 DATAANDANALYSES. 115 ADDITIONALTABLES.
    [Show full text]
  • Effect of Non-Steroidal Anti-Inflammatory Drugs (Nsaid) on the Rabbit Corneal Epithelium Studied by Scanning Electron Microscopy
    EFFECT OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAID) ON THE RABBIT CORNEAL EPITHELIUM STUDIED BY SCANNING ELECTRON MICROSCOPY STROOBANTS A.*, FABRE K.* AND MAUDGAL P. C.* SAMENVATTING: in the cell membranes and surface microvilli, or even exfoliation and necrosis of surface cells. The extent Het doel van deze studie is het effect van NSAID col- of cell damage appeared to be related to the active lyria te evalueren op het cornea- epitheel van de ogen ingredient in the eye drops, the pH of the solution, van 12 Nieuw-Zeeland konijnen. and the constituents of the vehicle, especially the Gedurende 1 week werden 12 Nieuw-Zeeland ko- type of preservative used. nijnen 5 maal per dag ingedruppeld met 6 gecom- mercialiseerde NSAID collyria. Elk collyrium werd ge- bruikt in 4 ogen. We onderzochten ook 2 controle RESUMÉ: cornea’s die niet ingedruppeld werden. Het epitheel werd geëvalueerd door een scanning electronen mi- Le but de cette étude est d’évaluer l’effet des gout- croscoop en de veranderingen werden gegradeerd tes NSAID sur l’épithélium cornéen des yeux de 12 met een empirisch score-systeem. Niet alleen het ac- lapins Néo-Zélandais. Pendant une semaine les 12 tief ingrediënt maar ook de bewaarmiddelen en een lapins Néo-Zélandais ont été instillés 5 fois par jour lage pH-waarde zijn belangrijke factoren van celbe- avec les 6 collyres NSAID commercialisés. Chaque schadiging. collyre a été utilisé dans 4 yeux. Nous avons exa- miné également 2 cornées, sans traitement. L’épi- thelium a été évalué par microscopie électronique à ABSTRACT: balayage et les changements ont été gradués sui- vant un système de score empirique.
    [Show full text]
  • Analgesic Anti-Inflammatory Adhesive Preparations
    Europaisches Patentamt (19) European Patent Office Office europeeneen des brevets EP 0 71 3 697 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) |nt Cl.e: A61K9/70 29.05.1996 Bulletin 1996/22 (21) Application number: 95307605.6 (22) Date of filing: 25.10.1995 (84) Designated Contracting States: • Orihara, Masamichi DE ES FR GB IT Minamisatama-gun Saitama-ken (JP) • Sugimoto, Yoshio (30) Priority: 26.10.1994 J P 284573/94 Saitama-ken (JP) • Yamazaki, Masaru (71) Applicant: Tokuhon Corporation Kitakatsushika-gun Saitama-ken (JP) Tokyo (JP) • Hoshino, Mitsunari Saitama-ken (JP) (72) Inventors: • Uchikawa, Masumasa • Sasaki, Yasuhiko Saitama-ken (JP) Saitama-ken (JP) • Arai, Hiroshi • Matsumura, Yukihiro Saitama-ken (JP) Saitama-ken (JP) • Imai, Susumu (74) Representative: Thomas, Roger Tamlyn et al Kitatsushika-gun Saitama-ken (JP) D. Young & Co. • Tooyama, Tetsuhiro 21 New Fetter Lane Saitama-ken (JP) London EC4A 1 DA (GB) (54) Analgesic anti-inflammatory adhesive preparations (57) A non-steroidal analgesic anti-inflammatory phenylyl)propionic acid and a modified copolymer in adhesive preparation obtained by coating one surface which methylmethacrylate is allowed to graft-polymer- of support with an adhesive containing S-(+)-2- ize on said copolymer, or with an adhesive containing ( 2-fluoro-4-biphenylyl)propionic acid and a styrene-iso- S-(+)-2-(2-fluoro-4-biphenylyl) propionic acid, sodium prene-styrene block copolymer or S-(+)-2-(2-fluor-4-bi- carboxymethyl cellulose and sodium polyacrylate. Is- O) CO CO o a. LU Printed by Jouve, 75001 PARIS (FR) EP 0 713 697 A1 Description The present invention concerns a non-steroidal analgesic anti-inflammatory adhesive preparation which contains as the pharmacologically effective component S-(+)-2-(2-fluoro-4-biphenylyl) propionic acid [abbreviated S-(+)-FP 5 hereinafter] which may be optically resolved from the racemic form 2-(2-fluoro-4-biphenylyl) propionic acid (also called: flurbiprofen).
    [Show full text]