DOCSLIB.ORG

Wo 2007/133751 A2

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Wo 2007/133751 A2 (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date (10) International Publication Number 22 November 2007 (22.11.2007) PCT WO 2007/133751 A2 (51) International Patent Classification: Not classified (74) Agents: NGUYEN, Sam, L. et al; Heller Ehrman LIp, 275 Middlefield Road, Menlo Park, CA 94025-3506 (US). (21) International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/US2007/01 1582 kind of national protection available): AE, AG, AL, AM, AT,AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, (22) International Filing Date: 14 May 2007 (14.05.2007) CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, (25) Filing Language: English IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY,MA, MD, ME, MG, MK, MN, MW, MX, (26) Publication Language: English MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, SV, SY, TJ, TM, (30) Priority Data: TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW 11/433,834 12 May 2006 (12.05.2006) US (84) Designated States (unless otherwise indicated, for every 11/607,593 1 December 2006 (0 1.12.2006) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (71) Applicant (for all designated States except US): ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), A.P.PHARMA, INC. [US/US]; 123 Saginaw Drive, European (AT,BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, Redwood City, CA 94063 (US). FR, GB, GR, HU, IE, IS, IT, LT,LU, LV,MC, MT, NL, PL, PT, RO, SE, SI, SK, TR), OAPI (BF, BJ, CF, CG, CI, CM, (72) Inventors; and GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG). (75) Inventors/Applicants (for US only): SHAH, Devang [IN/US]; 123 Saginaw Drive, Redwood City, CA 94063 Published: (US). BARR, John [GB/US]; 123 Saginaw Drive, Red — without international search report and to be republished wood City, CA 94063 (US). BAXTER, Brian [US/US]; upon receipt of that report 123 Saginaw Drive, Redwood City, CA 94063 (US). For two-letter codes and other abbreviations, refer to the "G uid HELLER, Jorge [US/US]; 8009 Dead Indian Memorial ance Notes on Codes and Abbreviations" appearing at the beg in Drive, Ashland, OR 97520 (US). ning of each regular issue of the PCT Gazette. (54) Title: BASE-STABILIZED POLYORTHOESTER FORMULATIONS (57) Abstract: A stabilized semi-solid delivery vehicle contains a polyorthoester and an excipient, and a pharmaceutical compo- sition contains an active agent, optionally a stabilizing agent, and the delivery vehicle. The pharmaceutical composition may be a topical, syringable, or injectable formulation; and is suitable for local delivery of the active agent. Methods of treatment are also disclosed. BASE-STABILIZED POLYORTHOESTER FORMULATIONS BACKGROUND OF THE INVENTION Field of the Invention [0001] This invention relates to stabilized semi-solid delivery vehicles comprising a polyorthoester and an excipient, and to controlled release pharmaceutical compositions comprising the delivery vehicle, optionally a stabilizing agent, and an active agent. The pharmaceutical compositions may be in the form of a topical, syringable, or injectable formulation for local controlled delivery of the active agent. Description of the Art [0002] A large class of active agents such as antibiotics, antiseptics, corticosteroids, anti-neoplasties, and local anesthetics may be administered to the skin or mucous membrane by topical application, or by injection. The active agent may act locally or systemically. Topical delivery may be accomplished through the use of compositions such as ointments, creams, emulsions, solutions, suspensions and the like. Injections for delivery of the active agents include solutions, suspensions and emulsions. All of these preparations have been extensively used for delivery of active agents for years. However, these preparations suffer the disadvantage that they are short-acting and therefore they often have to be administered several times in a day to maintain a therapeutically effective dose level in the blood stream at the sites where the activity/treatment is required. [0003] In recent years, a great deal of progress has been made to develop dosage forms which, after their administration, provide a long-term therapeutic response. These products may be achieved by microencapsulation, such as liposomes, microcapsules, microspheres, microparticles and the like. For this type of dosage forms, the active agents are typically entrapped or encapsulated in microcapsules, liposomes or microparticles which are then introduced into the body via injection or in the form of an implant. The release rate of the active agent from this type of dosage forms is controlled which eliminates the need for frequent dosing. However their manufacture is cumbersome which often results in high costs. In addition, they, in many cases, have low reproducibility and consequently lack of reliability in their release patterns. Furthermore, if an organic solvent is used in the manufacturing process, there could be organic solvent residues in the compositions which may be highly toxic. The use of an organic solvent is also undesirable for environmental and fire hazard reasons. [0004] Interest in synthetic biodegradable polymers for the delivery of therapeutic agents began in the early 1970's with the work of Yolles et al., Polymer News, 1, 9-15 (1970) using poly(lactic acid). Since that time, numerous other polymers have been prepared and investigated as bioerodible matrices for the controlled release of active agents. U.S. Patent Nos. 4,079,038, 4,093,709, 4,131,648, 4,138,344, 4,180,646, 4,304,767, 4,946,93 1 and 5,968,543 disclose various types of biodegradable or bioerodible polymers which may be used for controlled delivery of active agents. Many of these polymers may appear in the form of a semi-solid. However the semi-solid polymer materials are often too sticky. As a result, the active agents frequently cannot be easily and reliably released from the semi-solid polymer materials. SUMMARY OF THE INVENTION [0005] One embodiment of the present invention provides a semi-solid delivery vehicle which comprises a polyorthoester and an excipient. The excipient is readily miscible with the polyorthoester and the resulting semi-solid delivery vehicle has a smooth and flowable texture. The polyorthoesters suitable for the invention are represented by formulae I, II, III and IV below. [0006] Another embodiment of the present invention provides a controlled release semi-solid pharmaceutical composition for local controlled delivery of an active agent. The composition comprises an active agent and the semi-solid delivery vehicle. [0007] Another embodiment of the present invention provides a semi-solid syringable or injectable composition for the controlled delivery of locally acting active agents, in particular local anesthetics. [0008] In another embodiment, the above compositions comprising the polyorthoester can be homogeneously mixed with the excipient at room temperature without the use of a solvent. In another variation of the process, the polyorthoester can be homogeneously mixed with the excipient at between about 5 and 200 0C, more preferably between about 20 and 150 0C, and most preferably between about 25 and 100 0C. In one variation, the polyorthoester can be at one temperature, for example at about 7 00C, and the excipient can be at a different temperature, for example at about 120 0C, and the two components are mixed to attain a final temperature that is above room temperature. The desired temperatures for each of the two components will be based on the type of the polyorthoester and the excipient selected. The resulting semi-solid delivery vehicle and controlled-release pharmaceutical compositions have a useful texture and viscosity, and the release rate of the active agent from the compositions can also be conveniently and reliably adjusted to accommodate the desired therapeutic effect. [0009] Thus, in one aspect, this invention provides a semi-solid delivery vehicle, comprising: (i) a polyorthoester of formula I, formula II, formula III or formula IV IV where: R is a bond, -(CH2)a-, or -(CH2)b-O-(CH2)c-; where a is an integer of 1 to 10, and b and c are independently integers of 1 to 5; R* is a C i-4 alkyl; 0 R , R" and R'" are each independently H or C i-4 alkyl; n is an integer of at least 5; and A is R1, R3, or R4, where R1 is: where: p is an integer of 1 to 20; R3 and R6 are each independently: where: x is an integer of 0 to 30; y is an integer of 2 to 200; 8 R is hydrogen or C i- alkyl; 9 10 R and R are independently C 1- 12 alkylene; 1 12 1 12 R ' is hydrogen or C i- alkyl and R is C ]-6 alkyl; or R ' and R together are C3-10 alkylene; R4 is a diol containing at least one functional group independently selected from amide, imide, urea, and υrethane groups; and 5 R is hydrogen or C i-4 alkyl; and in which at least 0.01 mol percent of the A units are of the formula R 1, and wherein the polyorthoester has a lifetime of 12 hours or less in vitro. [0010] In another aspect, this invention provides a controlled release semi-solid pharmaceutical composition comprising: (a) a basic active agent; and (b) as a delivery vehicle, the semi-solid delivery vehicle described above. [0011] In another aspect, this invention provides a controlled release semi-solid pharmaceutical composition comprising: (a) an active agent; (b) a stabilizing agent; and (c) as a delivery vehicle, the semi-solid delivery vehicle described above.
Load more

Recommended publications
  • United States Patent (19) 11 Patent Number: 6,046,187 Berde Et Al
    US006046187A United States Patent (19) 11 Patent Number: 6,046,187 Berde et al. (45) Date of Patent: *Apr. 4, 2000 54) FORMULATIONS AND METHODS FOR 4,389,330 6/1983 Tice et al. .......................... 427/213.36 PROVIDING PROLONGED LOCAL 4,404,183 9/1983 Kawata et al. 424/19 ANESTHESIA 4,419,340 12/1983 Yolles ............. ... 424/19 4,434,153 2/1984 Urquhart et al. 424/22 (75) Inventors: Charles B. Berde, Brookline; Robert 4,479,911 10/1984 Fong - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 264/4.6 S. Langer, Newton, both of Mass.; 4,530,840 7/1985 Tice et al. ............................... 514/179 s s 4,542,025 9/1985 Tice et al. ................................. 424/78 Joanne Curley, San Jose, Calif.; Jenny 4,557,925 12/1985 Lindahl et al. ........................... 424/19 Castillo, Philadelphia, Pa. 4,568,535 2/1986 Loesche .................................... 424/19 4,568,536 2/1986 Kronenthal et al. 424/22 73 Assignee: Children's Medical Center 4,569,837 2/1986 Suzuki et al. ............................. 424/28 Corporation, Boston, Mass. 4,585,651 4/1986 Beck et al. ................................ 424/88 4,597,960 7/1986 Cohen ...... ... 424/28 * Notice: This patent issued on a continued pros- 4,622,219 11/1986 Haynes ...................................... 424/38 ecution application filed under 37 CFR 4,622,244 11/1986 Lapka et al. ....................... 427/213.32 1.53(d), and is subject to the twenty year 4,623.588 11/1986 Nuwayser et al. ................. 428/402.24 patent154(a)(2). term provisions of 35 U.S.C. ( List continued on next page.)page. FOREIGN PATENT DOCUMENTS 21 Appl.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 De Juan Et Al
    US 200601 10428A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 de Juan et al. (43) Pub. Date: May 25, 2006 (54) METHODS AND DEVICES FOR THE Publication Classification TREATMENT OF OCULAR CONDITIONS (51) Int. Cl. (76) Inventors: Eugene de Juan, LaCanada, CA (US); A6F 2/00 (2006.01) Signe E. Varner, Los Angeles, CA (52) U.S. Cl. .............................................................. 424/427 (US); Laurie R. Lawin, New Brighton, MN (US) (57) ABSTRACT Correspondence Address: Featured is a method for instilling one or more bioactive SCOTT PRIBNOW agents into ocular tissue within an eye of a patient for the Kagan Binder, PLLC treatment of an ocular condition, the method comprising Suite 200 concurrently using at least two of the following bioactive 221 Main Street North agent delivery methods (A)-(C): Stillwater, MN 55082 (US) (A) implanting a Sustained release delivery device com (21) Appl. No.: 11/175,850 prising one or more bioactive agents in a posterior region of the eye so that it delivers the one or more (22) Filed: Jul. 5, 2005 bioactive agents into the vitreous humor of the eye; (B) instilling (e.g., injecting or implanting) one or more Related U.S. Application Data bioactive agents Subretinally; and (60) Provisional application No. 60/585,236, filed on Jul. (C) instilling (e.g., injecting or delivering by ocular ion 2, 2004. Provisional application No. 60/669,701, filed tophoresis) one or more bioactive agents into the Vit on Apr. 8, 2005. reous humor of the eye. Patent Application Publication May 25, 2006 Sheet 1 of 22 US 2006/0110428A1 R 2 2 C.6 Fig.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 6,617,114 B1 Fowlkes Et Al
    USOO6617114B1 (12) United States Patent (10) Patent No.: US 6,617,114 B1 Fowlkes et al. (45) Date of Patent: Sep. 9, 2003 (54) IDENTIFICATION OF DRUG OTHER PUBLICATIONS COMPLEMENTARYLIBRARIES COMBINATORIAL Bottger, et al., Identification- Y - of novel mam2 binding peptides by phage display, Oncogene, vol. 13, pp. 2141-2147, 1996. (75) Inventors: Dana M. Fowlkes, Chapel Hill, NC Lu, et al., Expression of Thioredoxin Random Peptide (US); Brian K. Kay, Madison, WI Libraries On the Escherichia coli Cell Surface as Functional (US); Jeffrey A. Frelinger, Chapel Hill, Fusions to Flagellin. A System Designed for Exploring NC (US); Robin Parish Protein-Protein Interactions, Biotechnology, vol. 13, pp. Hyde-Deruyscher, Chapel Hill, NC 366-372, Apr. 1995. (US) Valadon, et al., Peptide Libraries Define the Fine Specificity of Antipolysaccharide Antibodies to Cryptococcus neofor mans, J. Mol. Biol., vol. 261, pp. 11-22, 1996. (73) Assignee: Karo Bio AB, Huddinge (SE) Giebel, L. et al., “Screening of Cyclic Peptide Phage Librar ies Identifies Ligands that Bind Streptavidin with High (*) Notice: Subject to any disclaimer, the term of this Affinities”, Biochemistry 34:15430–15435 (1995). patent is extended or adjusted under 35 Kay, Brian K., et al., “An M13 phage library displaying U.S.C. 154(b) by 0 days. random 38-amino-acid peptides as a Source of novel sequences with affinity to seleted targets', Gene 128:59-65 (21) Appl. No.: 09/069,827 (1993). Lam, Kit S. et al., “A new type of Synthetic peptide library for identifying ligand-binding activity' Nature 354:82-84 (22) Filed: Apr. 30, 1998 (1991).
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 6,264,917 B1 Klaveness Et Al
    USOO6264,917B1 (12) United States Patent (10) Patent No.: US 6,264,917 B1 Klaveness et al. (45) Date of Patent: Jul. 24, 2001 (54) TARGETED ULTRASOUND CONTRAST 5,733,572 3/1998 Unger et al.. AGENTS 5,780,010 7/1998 Lanza et al. 5,846,517 12/1998 Unger .................................. 424/9.52 (75) Inventors: Jo Klaveness; Pál Rongved; Dagfinn 5,849,727 12/1998 Porter et al. ......................... 514/156 Lovhaug, all of Oslo (NO) 5,910,300 6/1999 Tournier et al. .................... 424/9.34 FOREIGN PATENT DOCUMENTS (73) Assignee: Nycomed Imaging AS, Oslo (NO) 2 145 SOS 4/1994 (CA). (*) Notice: Subject to any disclaimer, the term of this 19 626 530 1/1998 (DE). patent is extended or adjusted under 35 O 727 225 8/1996 (EP). U.S.C. 154(b) by 0 days. WO91/15244 10/1991 (WO). WO 93/20802 10/1993 (WO). WO 94/07539 4/1994 (WO). (21) Appl. No.: 08/958,993 WO 94/28873 12/1994 (WO). WO 94/28874 12/1994 (WO). (22) Filed: Oct. 28, 1997 WO95/03356 2/1995 (WO). WO95/03357 2/1995 (WO). Related U.S. Application Data WO95/07072 3/1995 (WO). (60) Provisional application No. 60/049.264, filed on Jun. 7, WO95/15118 6/1995 (WO). 1997, provisional application No. 60/049,265, filed on Jun. WO 96/39149 12/1996 (WO). 7, 1997, and provisional application No. 60/049.268, filed WO 96/40277 12/1996 (WO). on Jun. 7, 1997. WO 96/40285 12/1996 (WO). (30) Foreign Application Priority Data WO 96/41647 12/1996 (WO).
    [Show full text]
  • Use of Topical Anesthetics for the Manufacture of A
    Europäisches Patentamt *EP000682514B1* (19) European Patent Office Office européen des brevets (11) EP 0 682 514 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.7: A61K 31/00, A61K 31/19, of the grant of the patent: A61K 31/135 12.09.2001 Bulletin 2001/37 (86) International application number: (21) Application number: 94907887.7 PCT/US94/00901 (22) Date of filing: 25.01.1994 (87) International publication number: WO 94/17790 (18.08.1994 Gazette 1994/19) (54) USE OF TOPICAL ANESTHETICS FOR THE MANUFACTURE OF A MEDICAMENT FOR THE TREATMENT OF BRONCHIAL ASTHMA VERWENDUNG VON LOKALANAESTHETIKA ZUR HERSTELLUNG EINES ARZNEIMITTELS ZUR BEHANDLUNG VON BRONCHIALASTHMA UTILISATION D’ANESTHESIANTS A USAGE LOCAL POUR LA REALISATION D’UN MEDICAMENT DESTINE AU TRAITEMENT DE L’ASTHME BRONCHIQUE (84) Designated Contracting States: (74) Representative: Matthews, Derek Peter et al AT BE CH DE DK ES FR GB GR IE IT LI LU MC NL Frank B. Dehn & Co., PT SE European Patent Attorneys, 179 Queen Victoria Street (30) Priority: 02.02.1993 US 12343 London EC4V 4EL (GB) (43) Date of publication of application: (56) References cited: 22.11.1995 Bulletin 1995/47 FR-M- 3 385 (73) Proprietor: MAYO FOUNDATION FOR MEDICAL • PNEUM.POL. vol. 50, no. 5-6 , 1982 pages 269 - EDUCATION AND RESEARCH 273 MARYLA KRASNOWSKA ET AL. ’A test of Rochester, MN 55905 (US) lidocaine usage in the treatment of bronchial asthma’ (72) Inventors: • KLIN.MED. vol. 45, no. 5 , 1967 page 50-54 • GLEICH, Gerald J. V.N.SAPEROV ’The treatment of bronchial Rochester, MN 55902 (US) asthma with the aid of intra-arterial injections of • OHNISHI, Tsukasa novocain’ Tokyo (JP) • RESPIRATION vol.
    [Show full text]
  • The Organic Chemistry of Drug Synthesis
    THE ORGANIC CHEMISTRY OF DRUG SYNTHESIS VOLUME 3 DANIEL LEDNICER Analytical Bio-Chemistry Laboratories, Inc. Columbia, Missouri LESTER A. MITSCHER The University of Kansas School of Pharmacy Department of Medicinal Chemistry Lawrence, Kansas A WILEY-INTERSCIENCE PUBLICATION JOHN WILEY AND SONS New York • Chlchester • Brisbane * Toronto • Singapore Copyright © 1984 by John Wiley & Sons, Inc. All rights reserved. Published simultaneously in Canada. Reproduction or translation of any part of this work beyond that permitted by Section 107 or 108 of the 1976 United States Copyright Act without the permission of the copyright owner is unlawful. Requests for permission or further information should be addressed to the Permissions Department, John Wiley & Sons, Inc. Library of Congress Cataloging In Publication Data: (Revised for volume 3) Lednicer, Daniel, 1929- The organic chemistry of drug synthesis. "A Wiley-lnterscience publication." Includes bibliographical references and index. 1. Chemistry, Pharmaceutical. 2. Drugs. 3. Chemistry, Organic—Synthesis. I. Mitscher, Lester A., joint author. II. Title. [DNLM 1. Chemistry, Organic. 2. Chemistry, Pharmaceutical. 3. Drugs—Chemical synthesis. QV 744 L473o 1977] RS403.L38 615M9 76-28387 ISBN 0-471-09250-9 (v. 3) Printed in the United States of America 10 907654321 With great pleasure we dedicate this book, too, to our wives, Beryle and Betty. The great tragedy of Science is the slaying of a beautiful hypothesis by an ugly fact. Thomas H. Huxley, "Biogenesis and Abiogenisis" Preface Ihe first volume in this series represented the launching of a trial balloon on the part of the authors. In the first place, wo were not entirely convinced that contemporary medicinal (hemistry could in fact be organized coherently on the basis of organic chemistry.
    [Show full text]
  • Ep 0932416 B1
    Europäisches Patentamt *EP000932416B1* (19) European Patent Office Office européen des brevets (11) EP 0 932 416 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.7: A61K 45/06, A61K 31/485, of the grant of the patent: A61K 31/165, A61K 31/135, 22.06.2005 Bulletin 2005/25 A61K 31/00, A61K 31/275 (21) Application number: 97910772.9 (86) International application number: PCT/US1997/017828 (22) Date of filing: 06.10.1997 (87) International publication number: WO 1998/015275 (16.04.1998 Gazette 1998/15) (54) METHOD AND POTENTIATED COMPOSITION FOR TREATING MIGRAINE VERFAHREN UND POTENZIERTE ZUSAMMENSETZUNG ZUR BEHANDLUNG VON MIGRÄNE THERAPIE ET COMPOSITION PHARMACEUTIQUE POTENTIALISEE EFFICACES CONTRE LA MIGRAINE (84) Designated Contracting States: • DHAVARE ET AL: "Effect of Drugs Influencing AT BE CH DE DK ES FI FR GB GR IE IT LI LU MC Central 5-HT Mechanisms on NL PT SE Amantadine-Induced Stereotyped Behaviour in the Rat" INDIAN JOURNAL PHYSIOL. (30) Priority: 09.10.1996 US 727923 PHARMACOL., vol. 27, no. 1, 1983, pages 19-24, 24.10.1996 US 736370 XP002058885 • MAJ T ET AL: "Antagonistic Effect of (43) Date of publication of application: Cyproheptadine on Neuroleptic-Induced 04.08.1999 Bulletin 1999/31 Catalepsy" PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, vol. 3, no. 1, 1975, pages 25-27, (73) Proprietor: Algos Pharmaceutical Corporation XP002058886 Neptune, NJ 07753 (US) • SKUZA ET AL: "Memantine, Amantadine and L-Deprenyl Potentiate the Action of L-DOPA in (72) Inventor: CARUSO, Frank, S. Monoamine-Depleted Rats" JOURNAL OF Colts Neck, NJ 07722 (US) NEURAL TRANSMISSION, vol.
    [Show full text]
  • Bbm:978-1-4684-7173-1/1.Pdf
    Index ACRYLONITRILE A Acetophenetidin, see: Phenacetin Abietic acid, detn - 464, 1590 Acetopropionic acid, see: Levulinic acid Abietic-type acids, detn - 70 Acetovanillone, detn - 150, 1211 Abietinic acid, see: Abietic acid Acetoxime, ref to spectrum - 1427 Acaricides, see individual com- p-Acetylaminobenzaldehyde thio- pounds semicarbazone, detn Accelerators (rubber) 696, 830, - 883, 1055 834, 849 Acetylcarbromal, detn - 1403 See also individual compounds Acetylcodeine - 1067 Acenaphthylene, detn - 63 Acetylene, detn in air - 1193 Acetal formation, spectral changes Acetylenes, CC'C , detn of traces due to - 320 5 - 1279 Acetaldehyde, detn Acetylenic compounds, detn as at 277 nm - 100 at 278 nm - 1185 mercuric acetate ad­ ducts - 1322 in acetic acid - 240 Acetylformic acid, see: Pyruvic as iodoform - 338 acid as thiosemicarbazone - 1271 Acetylisoniazid, detn - 110 in vinyl acetate - 241, 755, 3-Acetyl-6-methyl-2 ,4-pyrandione, 1090 p-Acetamidophenol, detn - 821, 822 see: Dehydroacetic 5-Acetamido-1,3,4-thiadiazole-2- acid thiol, detn - 824 N-Acetylmuramide glycahohydro­ Acetanilide, detn - 415, 1232 lase, see: Lysozyme Acetate, detn - 817 Acetylsalicyclic acid, Acetazolamide, detn - 760, 824 detn in drug mixt - 650, 750, Acetic acid, 880, 927, 1402, 1403, acetaldehyde in - 240 1404 hydrolysis of - 401 water in - 210 in phenobarbital - 280 Acetoacetate, detn - 1581 Acetoacetyl coenzyme A, detn - 461 mixt with salicylic acid - 261, Acetoacetyl thiol esters, absorption 1461 " a -Acids," detn in beer and wort of - 461 - 1226 Acetone, detn at 265 nm - 1185 Acids, organic, detn - 386 at 280 nm - 87 See also individual compounds in diacetone alcohol - 91 Aconite alkaloids, detn - 1019 as iodoform - 338, 1434 Acraldehyde, detn - 1185 in vinyl acetate 242, 1090 Acrilan, ref to reflectance spec- Acetone oxime, ref to spectrum - trum - 1455 1427 Acrolein, detn - 1185 3-(a-Acetonylbenzyl)-4-hydroxy- Acrylaldehyde, detn - 1185 coumarin, detn Acrylic acid - 852, 1334 at 308 nm - 304 Acrylonitrile ;.
    [Show full text]
  • US5276032.Pdf
    ||||||||||I|| USOO5276.032A United States Patent (19) 11 Patent Number: 5,276,032 King et al. 45) Date of Patent: Jan. 4, 1994 54 VISION AD AND ANESTHETC 56) References Cited COMPOSTON U.S. PATENT DOCUMENTS 1,907,392 5/1933 Stover ... ... 514/535 76) Inventors: O. Newton King, 2524 Yale Rd.; 2,382,546 8/1945 Curtis .... ... 54/535 X Henry W. Buck, 306 Homestead Dr., 2,803,582 8/1957 Cherney...... ... S4/535 X both of, Lawrence, Kans, 66049 3,019,163 1/1962 Harnist et al. ... 54/535 X 4,748,022 5/1988 Busciglio .......................... 424/95. FOREIGN PATENT DOCUMENTS 21 Appl. No.: 788,932 460629 1/1937 United Kingdom . Primary Examiner-Frederick E. Waddell 22) Fied: Nov. 7, 1991 Assistant Examiner-T. J. Criares 57 ABSTRACT Related U.S. Application Data A new visualizing and anesthetic composition and the process for the preparation thereof. The composition, 63 Continuation of Ser. No. 458,300, Dec. 28, 1989, aban generally as a gel, contains an effective amount of a doned. topical anesthetic, an effective amount of a visualizing agent and a pharmaceutically acceptable gelling reser 51 Int. Cl. ................. A61K 31/535; A61K 31/445; voir as a heat exchanger and/or a light transmitter. The A61K 31/24; A61K 47/00 composition is useful for topical application to a region (52) U.S. C. ................................. 514/239.2; 514/317; of mammalian skin to supply visualization to a lesion 514/535; 514/626, 514/536; 514/781; 514/944; therein and to anesthetize the region for a subsequent 514/967; 514/969 destructive therapy.
    [Show full text]
  • Ep 1646400 B1
    (19) & (11) EP 1 646 400 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 39/00 (2006.01) C07K 14/47 (2006.01) 21.07.2010 Bulletin 2010/29 A61P 37/06 (2006.01) A61P 37/08 (2006.01) (21) Application number: 04722319.3 (86) International application number: PCT/GB2004/001252 (22) Date of filing: 22.03.2004 (87) International publication number: WO 2004/082710 (30.09.2004 Gazette 2004/40) (54) TREATMENT OF ALLERGIC DISEASES USING A MODULATOR OF THE NOTCH SIGNALING PATHWAY BEHANDLUNG VON ALLERGISCHEN ERKRANKUNGEN UNTER VERWENDUNG EINES MODULATORS DES NOTCH SIGNALING PATHWAY TRAITEMENT DE MALADIES ALLERGIQUES UTILISANT UN MODULATEUR DE LA VOIE DE SIGNALISATION NOTCH (84) Designated Contracting States: (73) Proprietor: Celldex Therapeutics Limited AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Suite 54 HU IE IT LI LU MC NL PL PT RO SE SI SK TR Cambridge Designated Extension States: CB4 0EY (GB) LV (72) Inventors: (30) Priority: 21.03.2003 GB 0306583 • BODMER, Mark William, 21.03.2003 GB 0306582 Lorantis Limited 22.03.2003 GB 0306621 Cambridge CB4 0PE (GB) 22.03.2003 GB 0306622 • BRIEND, Emmanuel Cyrille Pascal, 22.03.2003 GB 0306626 Lorantis Limited 22.03.2003 GB 0306624 Cambridge CB4 OPE (GB) 22.03.2003 GB 0306640 • CHAMPION, Brian Robert, 22.03.2003 GB 0306644 Lorantis Limited 22.03.2003 GB 0306650 Cambridge CB4 0PE (GB) 22.03.2003 GB 0306651 • LENNARD, Andrew Christopher, 22.03.2003 GB 0306654 Lorantis Limited 04.04.2003 PCT/GB03/01525 Cambridge CB4 0PE (GB) 24.05.2003
    [Show full text]
  • United States Patent (19) 11 Patent Number: 5,747,060 Sackler Et Al
    US005747060A United States Patent (19) 11 Patent Number: 5,747,060 Sackler et al. 45) Date of Patent: May 5, 1998 54 PROLONGED LOCAL ANESTHESIA WITH IADR Abstracts 1982. Dental Research, 1990, Local Anes COLCHCNE thesia and Pain III, 3 pages. 75) Inventors: Richard Sackler, Greenwich; Paul Wall. et al., (Eds) Textbook of Pain, Third Edition, Publ. Goldenheim, Wilton, both of Conn.; Churchill Livingston, pp. 94-98. Mark Chasin, Manalapan, N.J. Devor. et al., 1991, A Group Report Mechanisms of Neu ropathic Pain Following Peripheral Injury, pp. 417-440. 73 Assignee: Euro-Celtique, S.A., Luxembourg. Luxembourg Devor, et al., 1983. Axoplasmic Transport Block Reduces Ectopic Impulse Generation in Injured Peripheral Nerves, 21 Appl. No.: 622,058 pp. 73-85. Schnebel. et al., The Use of Oral Colchicine for Low-Back 22 Filed: Mar. 26, 1996 Pain, 1987, pp. 354-357. (51) Int. Cl. ........................ A61K 9/14: A61K9/52 March, et al. Biodegradable Microspheres Containing a 52 U.S. Cl. ....................... 424/426; 424/195.1; 424/489: Colchicine Analogue Inhibit DNA Synthesis in Wascular 514/818: 514/825: 514/951; 514/963 Smooth Muscle Cells, 1994, pp. 1929-1933. 58) Field of Search ..................................... 514/818, 825. Dunn, et al. Monolithic Fibers For Controlled Delivery of 514/951, 963; 424/195.1, 489, 426 Tetracycline, 1980, pp. 157-159. (56) References Cited Lewis, et al. The Use Of In Vitro Release Methods to Guide the Development of Controlled-Release Formulations, U.S. PATENT DOCUMENTS Sourthern Research Institute. Alabama, pp. 61-64. 3,887,699 6/1975 Yoles ....................................... 424/19 Masters, et al., Prolonged Regional Nerve Blockade by 4001,388 1/1977 Shell ..
    [Show full text]
  • Chemical Structure-Related Drug-Like Criteria of Global Approved Drugs
    Molecules 2016, 21, 75; doi:10.3390/molecules21010075 S1 of S110 Supplementary Materials: Chemical Structure-Related Drug-Like Criteria of Global Approved Drugs Fei Mao 1, Wei Ni 1, Xiang Xu 1, Hui Wang 1, Jing Wang 1, Min Ji 1 and Jian Li * Table S1. Common names, indications, CAS Registry Numbers and molecular formulas of 6891 approved drugs. Common Name Indication CAS Number Oral Molecular Formula Abacavir Antiviral 136470-78-5 Y C14H18N6O Abafungin Antifungal 129639-79-8 C21H22N4OS Abamectin Component B1a Anthelminithic 65195-55-3 C48H72O14 Abamectin Component B1b Anthelminithic 65195-56-4 C47H70O14 Abanoquil Adrenergic 90402-40-7 C22H25N3O4 Abaperidone Antipsychotic 183849-43-6 C25H25FN2O5 Abecarnil Anxiolytic 111841-85-1 Y C24H24N2O4 Abiraterone Antineoplastic 154229-19-3 Y C24H31NO Abitesartan Antihypertensive 137882-98-5 C26H31N5O3 Ablukast Bronchodilator 96566-25-5 C28H34O8 Abunidazole Antifungal 91017-58-2 C15H19N3O4 Acadesine Cardiotonic 2627-69-2 Y C9H14N4O5 Acamprosate Alcohol Deterrant 77337-76-9 Y C5H11NO4S Acaprazine Nootropic 55485-20-6 Y C15H21Cl2N3O Acarbose Antidiabetic 56180-94-0 Y C25H43NO18 Acebrochol Steroid 514-50-1 C29H48Br2O2 Acebutolol Antihypertensive 37517-30-9 Y C18H28N2O4 Acecainide Antiarrhythmic 32795-44-1 Y C15H23N3O2 Acecarbromal Sedative 77-66-7 Y C9H15BrN2O3 Aceclidine Cholinergic 827-61-2 C9H15NO2 Aceclofenac Antiinflammatory 89796-99-6 Y C16H13Cl2NO4 Acedapsone Antibiotic 77-46-3 C16H16N2O4S Acediasulfone Sodium Antibiotic 80-03-5 C14H14N2O4S Acedoben Nootropic 556-08-1 C9H9NO3 Acefluranol Steroid
    [Show full text]