DOCSLIB.ORG

WO 2017/079765 Al 11 May 2017 (11.05.2017) W P O PCT

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
WO 2017/079765 Al 11 May 2017 (11.05.2017) W P O PCT (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 2017/079765 Al 11 May 2017 (11.05.2017) W P O PCT (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 31/437 (2006.01) A61K 45/06 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (21) International Application Number: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, PCT/US20 16/060868 DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, 7 November 2016 (07.1 1.2016) KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (25) Filing Language: English OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (26) Publication Language: English SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (30) Priority Data: ZW. 62/252,332 6 November 2015 (06. 11.2015) US 62/303,168 3 March 2016 (03.03.2016) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant: SAMUMED, LLC [US/US]; 9381 Judicial GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, Drive, Sute 1600, San Diego, CA 92121 (US). TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (72) Inventors: HOOD, John; 5124 Seagrove Court, San DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, Diego, California 92130 (US). WALLACE, David Mark; LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, 6448 Peinado Way, San Diego, California 92121 (US). SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, KC, Sunil Kumar; 10504 Clasico Court, San Diego, Cali GW, KM, ML, MR, NE, SN, TD, TG). fornia 92127 (US). YAZICI, Yusuf; 1921 Parkview Ter race, La Jolla, California 92037 (US). SWEARINGEN, Published: Christopher; 1668 Trenton Way, San Marcos, California — with international search report (Art. 21(3)) 92078-1074 (US). DELLAMARY, Luis A.; 829 Quiet Hills Dr., San Marcos, California 92069 (US). (74) Agents: FOLLETT, Angela D. et al; Fish & Richardson P.C., P.O. Box 1022, Minneapolis, Minnesota 55440-1022 (US). (54) Title: TREATMENT OF OSTEOARTHRITIS - (57) Abstract: Provided are compositions and methods for treating osteoarthritis including intra-articular administration of a com- pound of Formula (I) including amorphous and polymorph forms thereof. Treatment of Osteoarthritis CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application Serial Nos. 62/252,332, filed on November 6, 2015, and 62/303,168, filed on March 3, 2016, both of which are incorporated by reference in their entireties. TECHNICAL FIELD This description relates to compositions and methods for treating osteoarthritis including administration of a compound of Formula (I), including polymorph and amorphous forms thereof. For example, provided herein are methods for treating osteoarthritis including administration, such as intra-articular administration, of compositions prepared from and/or including compounds of Formula (I), including polymorph and amorphous forms thereof. BACKGROUND Osteoarthritis is a chronic degenerative joint disease in which cartilage and bone are primarily affected and for which acceptable long-term therapy does not yet exist. Osteoarthritis is especially common among people over 50 years of age, and usually affects ajoint on one side of the body. In osteoarthritis, the cartilage breaks down and wears away, causing pain, swelling, and loss of motion of the joint. Osteoarthritis of the knee can be unilateral, which affectsjust one knee joint in an individual, or bilateral, which affects both knees in the same individual. Reported prevalence of unilateral osteoarthritis has ranged from 12.6% - 34.1% in individuals with osteoarthritis [Ann. Rheum. Dis. (1998), 57(12), 717-723 and Joint Bone Spine (2011), 78(3), 275-278]. To date, clinical efforts aimed at treating osteoarthritis have been primarily directed toward symptomatic relief of pain and inflammation. SUMMARY Provided herein are methods for treating osteoarthritis in a subject in need thereof, the methods comprising intra-articular administration of a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I), including amorphous and polymorph forms thereof. Also provided herein is a method for treating osteoarthritis in a subject in need thereof, the method comprising intra-articular administration of a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I), wherein the compound of Formula (I) is substantially present as polymorph Form 13 having an X-ray powder diffraction pattern comprising peaks at °2Θ values of 6.4±0.2, 11.0±0.2, and 18.4±0.2. Also provided herein is a composition comprising a polymorph of a compound of Formula (I), wherein the polymorph is Form 1 and has an X-ray powder diffraction pattern comprising peaks at °2Θvalues of 6.8±0.2, 12.4±0.2, and 18.5±0.2; and wherein less than about 20% by weight of the amount of the compound of Formula (I) in the composition is polymorph Form 9 having X-ray powder diffraction pattern comprising peaks at °2Θvalues of 4.9±0.2, 18.6±0.2, and 21.1±0.2. Also provided herein is a composition comprising a mixture of polymorphs of a compound of Formula (I): wherein the mixture comprises a polymorph Form 1 having an X-ray powder diffraction pattern comprising peaks at °2Θvalues of 6.8±0.2, 12.4±0.2, and 18.5±0.2; and a non-stoichiometric hydrate of Form 1 having between 1% and about 20% by weight water; wherein less than about 20% by weight of the amount of the compound of Formula (I) in the composition is polymorph Form 9 having X-ray powder diffraction pattern comprising peaks at °2Θvalues of 4.9±0.2, 18.6±0.2, and 21.1±0.2. Also provided herein is a pharmaceutical composition comprising a compound of Formula (I), wherein the compound of Formula (I) is substantially present as a non- stoichiometric hydrate of Form 1 having between 1% and about 20% by weight water; and a pharmaceutically acceptable carrier; wherein less than about 20% by weight of the amount of the compound of Formula (I) in the composition is polymorph Form 9 having X-ray powder diffraction pattern comprising peaks at °2Θvalues of 4.9±0.2, 18.6±0.2, and 21.1±0.2. Also provided herein is a pharmaceutical composition comprising a compound of Formula (I), wherein the compound of Formula (I) is substantially present as polymorph Form 1 having an X-ray powder diffraction pattern comprising peaks at °2Θ values of 6.8±0.2, 12.4±0.2, and 18.5±0.2; and a pharmaceutically acceptable carrier; wherein less than about 20% by weight of the amount of the compound of Formula (I) in the composition is polymorph Form 9 having X-ray powder diffraction pattern comprising peaks at °2Θ values of 4.9±0.2, 18.6±0.2, and 21.1±0.2. Also provided herein is a pharmaceutical composition prepared by a process comprising mixing a pharmaceutically acceptable carrier and one or more polymorphs of a compound of Formula (I), wherein the polymorphs are selected from the group consisting of a polymorph Form 1 having an X-ray powder diffraction pattern comprising peaks at °2Θ values of 6.8±0.2, 12.4±0.2, and 18.5±0.2; a non-stoichiometric hydrate of Form 1 having between 1% and about 20% by weight water; wherein less than about 20% by weight of the amount of the compound of Formula (I) is polymorph Form 9 having X-ray powder diffraction pattern comprising peaks at °2Θ values of 4.9±0.2, 18.6±0.2, and 21.1±0.2. Also provided herein is a process for preparing a polymorph of a compound of Formula (I), wherein the polymorph is Form 1 and has an X-ray powder diffraction pattern comprising peaks at °2Θvalues of 6.8±0.2, 12.4±0.2, and 18.5±0.2; wherein the process comprises drying a compound of Formula (I) to Form 1. Also provided herein is a process for preparing a polymorph of a compound of Formula (I), wherein the polymorph is a non-stoichiometric hydrate of Form 1 having between 1% and about 20% by weight water; wherein the process comprises reslurrying a compound of Formula (I) in an aqueous solution. Also provided herein is a method for treating osteoarthritis in a subject in need thereof, the method comprising intraarticular administration of a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof; wherein the compound of Formula (I) is substantially present as a non-stoichiometric hydrate of Form 1 having between 1% and 20% by weight water. Also provided herein is a composition comprising a polymorph of a compound of Formula (I), wherein the polymorph is a non-stoichiometric hydrate and has an X-ray powder diffraction pattern comprising peaks at °2Θ values of 6.4±0.2, 11.0±0.2, and 18.4±0.2; and wherein less than about 20% by weight of the amount of the compound of Formula (I) in the composition is polymorph Form 9 having X-ray powder diffraction pattern comprising peaks at °2Θvalues of 4.9±0.2, 18.6±0.2, and 21.1±0.2.
Load more

Recommended publications
  • So2 and Wine: a Review
    OIV COLLECTIVE EXPERTISE DOCUMENT SO2 AND WINE: A REVIEW SO2 AND WINE: A REVIEW 1 MARCH 2021 OIV COLLECTIVE EXPERTISE DOCUMENT SO2 AND WINE: A REVIEW WARNING This document has not been submitted to the step procedure for examining resolutions and cannot in any way be treated as an OIV resolution. Only resolutions adopted by the Member States of the OIV have an official character. This document has been drafted in the framework of Expert Group “Food safety” and revised by other OIV Commissions. This document, drafted and developed on the initiative of the OIV, is a collective expert report. © OIV publications, 1st Edition: March 2021 (Paris, France) ISBN 978-2-85038-022-8 OIV - International Organisation of Vine and Wine 35, rue de Monceau F-75008 Paris - France www.oiv.int 2 MARCH 2021 OIV COLLECTIVE EXPERTISE DOCUMENT SO2 AND WINE: A REVIEW SCOPE The group of experts « Food safety » of the OIV has worked extensively on the safety assessment of different compounds found in vitivinicultural products. This document aims to gather more specific information on SO2. This document has been prepared taking into consideration the information provided during the different sessions of the group of experts “Food safety” and information provided by Member States. Finally, this document, drafted and developed on the initiative of the OIV, is a collective expert report. This review is based on the help of scientific literature and technical works available until date of publishing. COORDINATOR OIV - International Organisation of Vine and Wine AUTHORS Dr. Creina Stockley (AU) Dr. Angelika Paschke-Kratzin (DE) Pr.
    [Show full text]
  • Sulfite: Here, There, Everywhere
    Sulfite: Here, There, Everywhere Max T. Baker, PhD Associate Professor Department of Anesthesia University of Iowa Inadvertent Exposures Combustion of fossil fuels, Air pollutant Large quantities as sulfur dioxide are expelled from volcanos Kilauea on the Big Island Small quantities endogenously formed in mammals from sulfur-containing amino acid metabolism Deliberate Exposures As Preservative- Wine, Beer (dates to Roman times From burning sulfur candles) Fruits and Vegetables (reduce browning, extend shelf-life) Pharmaceuticals1 Reductant - Antioxidant - Antimicrobial What are Sulfites? Oxidized Forms of the Sulfur Atom Sulfur Dioxide, MW = 64, bp = - 10oC (gaseous) Sulfur (IV) - Oxidation state of 4 S = Atomic number 16 – electrons/shell, 2,8,6 Sodium Dioxide Readily Hydrates2 Sulfur Carbon Dioxide Dioxide (irritant) H O H2O 2 Sulfurous Unstable Carbonic low acid species acid pH high pH Bisulfite Bicarbonate anion anion Sulfite Carbonate dianion dianion Forms radical Doesn’t form radical Bisulfite Can Combine with SO2 to form Metabisulfite + excess Bisulfite Metabisulfite (disulfite, pyrosulfite) “Sulfite” usually added to drugs as sodium or potassium salts of: Sulfite, Bisulfite, or Metabisulfite Endogenous to Mammals Small quantities formed from sulfur-containing amino acid metabolism - cysteine, methionine3 + - + H2O + 2H + 2 e Sulfite Sulfate Rapidly detoxified by sulfite oxidase (SOX) to form sulfate – a two electron oxidation, molybdenum dependent Two Confirmed Sulfite Toxicities Neurological abnormalities from genetic sulfite oxidase deficiency3 Allergic reactions from exogenous exposure4 Oral, parenteral, inhalational exposure: dermatitis, urticaria, flushing, hypotension, abdominal pain and diarrhea to life- threatening anaphylactic and asthmatic reactions “The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people." - FDA Prevalence – 3-10% are sulfite sensitive among asthmatic subjects.
    [Show full text]
  • Classification Decisions Taken by the Harmonized System Committee from the 47Th to 60Th Sessions (2011
    CLASSIFICATION DECISIONS TAKEN BY THE HARMONIZED SYSTEM COMMITTEE FROM THE 47TH TO 60TH SESSIONS (2011 - 2018) WORLD CUSTOMS ORGANIZATION Rue du Marché 30 B-1210 Brussels Belgium November 2011 Copyright © 2011 World Customs Organization. All rights reserved. Requests and inquiries concerning translation, reproduction and adaptation rights should be addressed to [email protected]. D/2011/0448/25 The following list contains the classification decisions (other than those subject to a reservation) taken by the Harmonized System Committee ( 47th Session – March 2011) on specific products, together with their related Harmonized System code numbers and, in certain cases, the classification rationale. Advice Parties seeking to import or export merchandise covered by a decision are advised to verify the implementation of the decision by the importing or exporting country, as the case may be. HS codes Classification No Product description Classification considered rationale 1. Preparation, in the form of a powder, consisting of 92 % sugar, 6 % 2106.90 GRIs 1 and 6 black currant powder, anticaking agent, citric acid and black currant flavouring, put up for retail sale in 32-gram sachets, intended to be consumed as a beverage after mixing with hot water. 2. Vanutide cridificar (INN List 100). 3002.20 3. Certain INN products. Chapters 28, 29 (See “INN List 101” at the end of this publication.) and 30 4. Certain INN products. Chapters 13, 29 (See “INN List 102” at the end of this publication.) and 30 5. Certain INN products. Chapters 28, 29, (See “INN List 103” at the end of this publication.) 30, 35 and 39 6. Re-classification of INN products.
    [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]
  • Sulfur Dioxide and Some Sulfites, Bisulfites and Metabisulfites
    SULFUR DIOXIDE AND SOME SULFITES, BISULFITES AND METABISULFITES 1. Exposure Data 1.1 Chemical and physical data 1.1.1 Synonyms and structural and molecular data Sulfr dioxi Chem. Abstr. Serv Reg. No.: 7446-09-5 Replaced CAS Nos.: 8014-94-6; 12396-99-5; 83008-56-4; 89125-89-3 Chem. Abstr. Name; Sulfur dioxide IUPAC Systematic Name: Sulfur dioxide Synonyms: Sulfurous acid anhydride; sulfurous anhydride; sulfurous oxide; sulfur oxide (S02); sulfur superoxide; sulphur dioxide 0=8=0 S02 MoL. wt: 64.07 Sodium sulfte Chem. Abstr. Serv Reg. No.: 7757-83-7 Altemate CAS No.: 10579-83-6 Replaced CAS No.: 68135-69-3 Chem. Abstr. Name: Sulfurous acid, di sodium salt IUPAC Systematic Name: Sulfurous acid, disodium salt Synonyms: Anhydrous sodium sulfite; disodium sulfite; sodium sulphite o 1/ Na · 0 - 8 - 0 · Na Na2S0J MoL. wt: 126.04 Sodium bisulfe Chem. Abstr. Serv Reg. No.: 7631-90-5 Replaced CAS Nos.: 57414-01-4; 69098-86-8; 89830-27-3; 91829-63-9 Chem. Abstr. Name: Sulfurous acid, monosodium salt IUPAC Systematic Name: Sulfurous acid, monosodium salt -131- 132 lARe MONOGRAPHS VOLUME 54 Synonyms: Hydrogen sulfite sodium; monosodium sulfite; sodium acid sulfite; sodium bisulphite; sodium hydrogen sulfite; sodium sulfite (NaHS03) o Il HO - S - a · Na NaHS03 MoL. wt: 104.06 Sodium metabisulfte Chem. Abstr. Serv Reg. No.: 7681-57-4 Altemate CAS No.: 7757-74-6 Replaced CAS No.: 15771-29-6 Chem. Abstr. Name: Disulfurous acid, disodium salt IUPAC Systematic Name: Pyrosulfurous acid, disodium salt Synonyms: Disodium disulfite; disodium metabisulfite; disodium pyrosulfite; sodium disulfite; sodium metabisulphite; sodium pyrosulfite oIl Il0 Na · 0- S - a - S - a · Na .Na2S20S MoL.
    [Show full text]
  • Ion Channels in Pulmonary Hypertension: a Therapeutic Interest?
    International Journal of Molecular Sciences Review Ion Channels in Pulmonary Hypertension: A Therapeutic Interest? Mélanie Lambert 1,2,3,Véronique Capuano 1,2,3, Andrea Olschewski 4,5, Jessica Sabourin 6, Chandran Nagaraj 4, Barbara Girerd 1,2,3, Jason Weatherald 1,2,3,7,8, Marc Humbert 1,2,3 and Fabrice Antigny 1,2,3,* 1 Univ. Paris-Sud, Faculté de Médecine, 94270 Kremlin-Bicêtre, France; [email protected] (M.L.); [email protected] (V.C.); [email protected] (B.G.); [email protected] (J.W.); [email protected] (M.H.) 2 AP-HP, Centre de Référence de l’Hypertension Pulmonaire Sévère, Département Hospitalo-Universitaire (DHU) Thorax Innovation, Service de Pneumologie et Réanimation Respiratoire, Hôpital de Bicêtre, 94270 Le Kremlin-Bicêtre, France 3 UMRS 999, INSERM and Univ. Paris–Sud, Laboratoire d’Excellence (LabEx) en Recherche sur le Médicament et l’Innovation Thérapeutique (LERMIT), Hôpital-Marie-Lannelongue, 92350 Le Plessis Robinson, France 4 Ludwig Boltzmann Institute for Lung Vascular Research, Stiftingtalstrasse 24, Graz 8010, Austria; [email protected] (A.O.); [email protected] (C.N.) 5 Department of Physiology, Medical University Graz, Neue Stiftingtalstraße 6, Graz 8010, Austria 6 Signalisation et Physiopathologie Cardiovasculaire, UMRS 1180, Univ. Paris-Sud, INSERM, Université Paris-Saclay, 92296 Châtenay-Malabry, France; [email protected] 7 Division of Respirology, Department of Medicine, University of Calgary, Calgary, AB T1Y 6J4, Canada 8 Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB T1Y 6J4, Canada * Correspondence: [email protected]; Tel.: +33-1-4094-2299; Fax: +33-1-4094-2522 Received: 30 July 2018; Accepted: 8 October 2018; Published: 14 October 2018 Abstract: Pulmonary arterial hypertension (PAH) is a multifactorial and severe disease without curative therapies.
    [Show full text]
  • Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0192440 A1
    US 20190192440A1 (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0192440 A1 LI (43 ) Pub . Date : Jun . 27 , 2019 ( 54 ) ORAL DRUG DOSAGE FORM COMPRISING Publication Classification DRUG IN THE FORM OF NANOPARTICLES (51 ) Int . CI. A61K 9 / 20 (2006 .01 ) ( 71 ) Applicant: Triastek , Inc. , Nanjing ( CN ) A61K 9 /00 ( 2006 . 01) A61K 31/ 192 ( 2006 .01 ) (72 ) Inventor : Xiaoling LI , Dublin , CA (US ) A61K 9 / 24 ( 2006 .01 ) ( 52 ) U . S . CI. ( 21 ) Appl. No. : 16 /289 ,499 CPC . .. .. A61K 9 /2031 (2013 . 01 ) ; A61K 9 /0065 ( 22 ) Filed : Feb . 28 , 2019 (2013 .01 ) ; A61K 9 / 209 ( 2013 .01 ) ; A61K 9 /2027 ( 2013 .01 ) ; A61K 31/ 192 ( 2013. 01 ) ; Related U . S . Application Data A61K 9 /2072 ( 2013 .01 ) (63 ) Continuation of application No. 16 /028 ,305 , filed on Jul. 5 , 2018 , now Pat . No . 10 , 258 ,575 , which is a (57 ) ABSTRACT continuation of application No . 15 / 173 ,596 , filed on The present disclosure provides a stable solid pharmaceuti Jun . 3 , 2016 . cal dosage form for oral administration . The dosage form (60 ) Provisional application No . 62 /313 ,092 , filed on Mar. includes a substrate that forms at least one compartment and 24 , 2016 , provisional application No . 62 / 296 , 087 , a drug content loaded into the compartment. The dosage filed on Feb . 17 , 2016 , provisional application No . form is so designed that the active pharmaceutical ingredient 62 / 170, 645 , filed on Jun . 3 , 2015 . of the drug content is released in a controlled manner. Patent Application Publication Jun . 27 , 2019 Sheet 1 of 20 US 2019 /0192440 A1 FIG .
    [Show full text]
  • Download Product Insert (PDF)
    PRODUCT INFORMATION Polmacoxib Item No. 17509 OO CAS Registry No.: 301692-76-2 Formal Name: 4-[3-(3-fluorophenyl)-4,5-dihydro-5,5-dimethyl- S NH 4-oxo-2-furanyl]-benzenesulfonamide 2 MF: C H FNO S 18 16 4 O FW: 361.4 Purity: ≥98% F UV/Vis.: λmax: 238, 320 nm Supplied as: A crystalline solid O Storage: -20°C Stability: ≥2 years Information represents the product specifications. Batch specific analytical results are provided on each certificate of analysis. Laboratory Procedures Polmacoxib is supplied as a crystalline solid. A stock solution may be made by dissolving the polmacoxib in the solvent of choice. Polmacoxib is soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide (DMF), which should be purged with an inert gas. The solubility of polmacoxib in ethanol is approximately 5 mg/ml and approximately 20 mg/ml in DMSO and DMF. Polmacoxib is sparingly soluble in aqueous buffers. For maximum solubility in aqueous buffers, polmacoxib should first be dissolved in DMSO and then diluted with the aqueous buffer of choice. Polmacoxib has a solubility of approximately 0.5 mg/ml in a 1:8 solution of DMSO:PBS (pH 7.2) using this method. We do not recommend storing the aqueous solution for more than one day. Description Polmacoxib is an inhibitor of cyclooxygenase 2 (COX-2) and the carbonic anhydrase subtypes I (CAI) and 1 CAII. It inhibits COX-2 in the absence of carbonic anhydrase II with an IC50 value of 40 nM, which increases by approximately 4- and 17-fold in the presence of a CAII at a molar ratio of 1:1 and 1:5, respectively.2 It also inhibits CAI and CAII (IC50s = 210 and 95 nM, respectively).
    [Show full text]
  • Analgesic & Rheumatology
    Recommendations of the SEC (Analgesic & Rheumatology) made in its 72nd meeting held on 24.06.2021 & 25.06.2021 at CDSCO HQ New Delhi. File Name & Recommendations Agenda Drug Name, Firm Name No Strength New Drugs Division ND/MA/21/000076 M/s Hetero Labs Ltd. The firm presented their proposal of Polmacoxib 2 mg Fresh Application Phase III clinical trial protocol capsules along with BE study protocol before committee. After detailed deliberation, the 1. committee recommended for grant of permission to conduct the BE study. The firm should present the results of BE study before committee for further consideration of phase III clinical trial protocol. Biological Division BIO/CT- The firm presented their proposal 18/FF/2021/24609- for marketing authorization and Belimumab (Marketing Authorization)- local clinical trial waiver based on Belimumab the results of GCT including sub set analysis on 66 Indian patients. The committee noted that the drug is not an unmet need in the country. M/s. GSK Further, the data presented by the 2. Pharmaceuticals firm in Indian sub-set is limited and Ltd. in different route of administration (intravenous) while the firm is seeking MA for subcutaneous route. After detailed deliberation, the committee did not recommend for grant of approval for marketing authorization. BIO/CT21/FF/2021/246 M/s Reliance Life The firm presented their proposal 79- Denosumab Sciences Pvt ltd for marketing authorization along 60mg/ml with the results of Phase-III clinical trial. 3. The committee noted that the Phase III trial was approved
    [Show full text]
  • TRP Channel Transient Receptor Potential Channels
    TRP Channel Transient receptor potential channels TRP Channel (Transient receptor potential channel) is a group of ion channels located mostly on the plasma membrane of numerous human and animal cell types. There are about 28 TRP channels that share some structural similarity to each other. These are grouped into two broad groups: Group 1 includes TRPC ("C" for canonical), TRPV ("V" for vanilloid), TRPM ("M" for melastatin), TRPN, and TRPA. In group 2, there are TRPP ("P" for polycystic) and TRPML ("ML" for mucolipin). Many of these channels mediate a variety of sensations like the sensations of pain, hotness, warmth or coldness, different kinds of tastes, pressure, and vision. TRP channels are relatively non-selectively permeable to cations, including sodium, calcium and magnesium. TRP channels are initially discovered in trp-mutant strain of the fruit fly Drosophila. Later, TRP channels are found in vertebrates where they are ubiquitously expressed in many cell types and tissues. TRP channels are important for human health as mutations in at least four TRP channels underlie disease. www.MedChemExpress.com 1 TRP Channel Antagonists, Inhibitors, Agonists, Activators & Modulators (-)-Menthol (E)-Cardamonin Cat. No.: HY-75161 ((E)-Cardamomin; (E)-Alpinetin chalcone) Cat. No.: HY-N1378 (-)-Menthol is a key component of peppermint oil (E)-Cardamonin ((E)-Cardamomin) is a novel that binds and activates transient receptor antagonist of hTRPA1 cation channel with an IC50 potential melastatin 8 (TRPM8), a of 454 nM. Ca2+-permeable nonselective cation channel, to 2+ increase [Ca ]i. Antitumor activity. Purity: ≥98.0% Purity: 99.81% Clinical Data: Launched Clinical Data: No Development Reported Size: 10 mM × 1 mL, 500 mg, 1 g Size: 10 mM × 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg (Z)-Capsaicin 1,4-Cineole (Zucapsaicin; Civamide; cis-Capsaicin) Cat.
    [Show full text]
  • Concomitant Use of Nsaids Or Ssris with Noacs Requires Monitoring for Bleeding
    Original Article Yonsei Med J 2020 Sep;61(9):741-749 https://doi.org/10.3349/ymj.2020.61.9.741 pISSN: 0513-5796 · eISSN: 1976-2437 Concomitant Use of NSAIDs or SSRIs with NOACs Requires Monitoring for Bleeding Min-Taek Lee1, Kwang-Yeol Park2, Myo-Song Kim1, Seung-Hun You1, Ye-Jin Kang1, and Sun-Young Jung1 1College of Pharmacy, Chung-Ang University, Seoul; 2Department of Neurology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea. Purpose: Non-vitamin K antagonist oral anticoagulants (NOACs) are widely used in patients with atrial fibrillation (AF) because of their effectiveness in preventing stroke and their better safety, compared with warfarin. However, there are concerns for an in- creased risk of bleeding associated with concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) or selective sero- tonin reuptake inhibitors (SSRIs) with NOACs. In this study, we aimed to evaluate the risk of bleeding events in individuals taking concomitant NSAIDs or SSRIs with NOACs after being diagnosed with AF. Materials and Methods: A nested case-control analysis to assess the safety of NSAIDs and SSRIs among NOAC users with AF was performed using data from Korean National Health Insurance Service from January 2012 to December 2017. Among patients who were newly prescribed NOACs, 1233 cases hospitalized for bleeding events were selected, and 24660 controls were determined. Results: The risk of bleeding events was higher in patients receiving concomitant NSAIDs [adjusted odds ratio (aOR) 1.41; 95% confidence interval (CI) 1.24–1.61] or SSRIs (aOR 1.92; 95% CI 1.52–2.42) with NOACs, compared to no use of either drug, respec- tively.
    [Show full text]
  • Directory of Korean Pharmaceutical Industry 2016
    2016 Directory of Korean Pharmaceutical Industry Contents 1. Greeting ������������������������������������������������������������������������������������������������������������������������������������������� 4 2. Overview of the Korean Pharmaceutical Industry ������������������������������������������������������������ 6 1) Current Status 2) Production Management System 3) Development of New Drugs 4) R&D Reinforcement 5) Biopharmaceuticals 6) Globalization 7) Korean Pharmaceutical Industry Vision - PHARMA 2020 3. Directory of Pharmaceutical Companies �������������������������������������������������������������������������� 13 · Regular Members(2015. 4) A~D ���������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 14 E~J ��������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 66 K~P �������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 110 R~Y �������������������������������������������������������������������������������������������������������������������������������������������������������������������������� 158 · Associated Members(2015. 4) C~G ���������������������������������������������������������������������������������������������������������������������������������������������������������������������������
    [Show full text]