DOCSLIB.ORG

(19) United States (12) Patent Application Publication (10) Pub

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(19) United States (12) Patent Application Publication (10) Pub US 20120129819A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0129819 A1 Vancaillie et al. (43) Pub. Date: May 24, 2012 (54) GEL COMPOSITIONS FOR Publication Classi?cation ADMINISTRATION OF (51) Int Cl PHARMACEUTICALLY ACTIVE A 61K 31/565 (200601) COMPOUNDS A61P 31/00 (2006.01) A61P 29/00 2006.01 (75) Inventors: Thierry Vancaillie, Castlecrag A 611, 5/24 g2oo6~olg (AU), Alan Hewitt, Wrexham (GB) A611) 13/00 (200601) A61P 23/00 2006.01 (73) Assignee: Medortus (UK) Ltd, Wrexham A611; 25/04 E200601; (GB) A61P 1 7/00 (2006.01) A61P 15/00 (2006.01) (21) Appl' No" 13/264311 (52) us. Cl. ........................ .. 514/170; 514/182; 514/171 (22) PCT Filed: Apr. 14, 2010 (57) ABSTRACT (86) PCT No... PCT/AU10/00408 The P resent invention P rovides a P harmaceutical com P osition in the form of a Water-based gel comprising: at least one § 371 (6X1), pharmaceutically active compound; at least one gelling agent; (2)’ (4) Date; Feb 9, 2012 a solubilising agent; and Water, Wherein said composition is free or substantially free of unsubstituted monohydric alco (30) Foreign Application Priority Data hols having between 1 and 6 carbon atoms. The invention also relates to methods for preparing the compositions and uses Apr. 14, 2009 (AU) .............................. .. 2009901585 thereof. US 2012/0129819 A1 May 24, 2012 GEL COMPOSITIONS FOR ders (such as skin disorders), a compound useful in the con ADMINISTRATION OF trol of infection, a compound useful in the treatment of PHARMACEUTICALLY ACTIVE in?ammatory conditions, a compound useful in the treatment COMPOUNDS of sexual dysfunction, a compound useful in the treatment of urological disorders, a compound useful in anaesthesia, an TECHNICAL FIELD analgesic compound, a compound Which is an ot-adrenergic [0001] The present invention relates to Water-based gel receptor agonist, a hormone or a prohormone. compositions comprising at least one pharmaceutically active [0015] The hormone may be a sex hormone, a thyroid hor compound, and also to methods of administering the compo mone or a groWth hormone. sitions. [0016] The sex hormone may be an estrogen (for example estriol), an androgen (for example testosterone) or a proge BACKGROUND OF THE INVENTION stagen. [0017] The hormone may be a hormone used in hormone [0002] A major dif?culty encountered With pharmaceutical replacement therapy. compounds, particularly those of higher molecular Weight, is [0018] In one embodiment, the hormone is a natural or that they are insoluble in aqueous solution. Because the bio synthetic estrogen, for example estriol, estrone or estradiol. availability and hence e?icacy of many pharmaceutical com [0019] The composition may comprise at least tWo phar pounds is largely dependent on their presence in a soluble maceutically active compounds selected from the group con form, the formulation of Water-insoluble compounds in aque sisting of: a natural or synthetic estrogen, an analgesic com ous delivery vehicles is problematic. pound, a compound useful in anaesthesia and an ot-adrenergic [0003] In the context of topical delivery vehicles this prob receptor agonist. lem has been addressed by the incorporation of an organic [0020] The composition may comprise at least tWo phar solvent into the vehicle Which improves the solubility of the maceutically active compounds, Wherein one of the pharma Water-insoluble compound(s), and hence increases bioavail ceutically active compounds is a natural or synthetic estro ability. Where the Water-insoluble compounds are steroid gen, and the other pharmaceutically active compound(s) hormones loWer alcohols (i.e. alcohols having betWeen 1 and is/are selected from the group consisting of: an analgesic 6 carbon atoms) are typically used to enhance solubility. compound, a compound useful in anaesthesia and an ot-adr HoWever, loWer alcohols such as ethanol have the undesired energic receptor agonist. effect of drying skin as a result of solubilisation of the hydro [0021] The analgesic compound may be tramadol, the com phobic components thereof. In addition, stinging also occurs pound useful in anaesthesia may be aicaine anaesthetic and When loWer alcohols come into contact With sensitive mem the ot-adrenergic receptor agonist may be clonidine. branes such as the vagina. A further problem associated With [0022] The hormone or prohor'mone may be selected from the use of ethanol is that it cannot be included in halal medi the group consisting of: thyroxine, diiodothyrosine, melato cations. nin, epinephrine, natural and synthetic estrogens, dehydroe [0004] There is therefore a need for compositions Wherein piandrosterone, ketodehydroepiandrosterone, testosterone, Water-insoluble compounds can be effectively solubilised in progesterone and human groWth hormone. the absence of loWer alcohols. [0023] The at least one pharmaceutically active compound may be a steroidal compound. SUMMARY OF THE INVENTION [0024] The at least one gelling agent may be selected from [0005] In a ?rst aspect, the present invention provides a the group consisting of: algae extracts, gums, polysaccha pharmaceutical composition in the form of a Water-based gel rides, starches, pectins, hydrolysed proteins, cellulose deriva comprising: tives and polymers comprising pendant carboxylic acid [0006] (i) at least one pharmaceutically active compound; groups, or esters thereof, or comprising pendant anhydrides [0007] (ii) at least one gelling agent; of dicarboxylic acid groups and block co-polymers based on [0008] (iii) a solubilising agent; and ethylene oxide and/or propylene oxide. The gelling agent [0009] (iv) Water, may be natural, synthetic or semi-synthetic. Wherein said composition is free or substantially free of [0025] In one embodiment, the gelling agent may be unsubstituted monohydric alcohols having betWeen 1 and 6 selected from the group consisting of: polymers comprising carbon atoms. pendant carboxylic acid groups, or esters thereof, or compris [0010] The at least one pharmaceutically active compound ing pendant anhydrides of dicarboxylic acid groups and block may be present in the composition in an amount betWeen co-polymers based on ethylene oxide and/or propylene oxide. about 0.0005% (W/W) and about 25% (W/W), or betWeen [0026] The gelling agent may be a carbomer. about 0.001% (W/W) and about 5% (W/W). [0027] The carbomer may be a polymer of acrylic acid [0011] The at least one pharmaceutically active compound cross-linked With polyalkenyl ethers or divinyl glycol. may be a compound Which is insoluble in Water or sparingly [0028] The carbomer may be a copolymer of acrylic acid soluble in Water. and long chain alkyl acrylates crosslinked With polyalkenyl [0012] The composition may further comprise at least one ethers. pharmaceutically active compound Which is soluble in Water. [0029] The gelling agent may be present in the composition [0013] The at least one pharmaceutically active compound in an amount betWeen about 0.01% (W/W) and about 50% may be any compound Which provides a therapeutic bene?t or (W/W), or betWeen about 0.05% (W/W) and about 10% (W/W). a cosmetic bene?t to a subject. [0030] The solubilising agent may be selected from the [0014] The at least one pharmaceutically active compound group consisting of pyrrolidone or a derivative thereof, castor may be a compound active in the gynaecological ?eld, a oil, polyethoxylated castor oil, diethylene glycol monoethyl compound useful in the treatment of epithelial tissue disor ether, propylene glycol caprylate, propylene glycol mono US 2012/0129819 A1 May 24, 2012 caprylate, medium chain glycerides, 2-methacryloxyeth ily solely”. Furthermore, variations of the Word “compris ylphosphonylcholine, cyclodextrins and derivatives thereof, ing”, such as “comprise” and “comprises”, have correspond lecithin, polysorbates, PEG-phospholipids, phospholipids, ingly varied meanings. cholesterol-PEG and saturated polyglycolised CS-Cl0 glyc [0053] In the context of the present speci?cation, the term erides. “unsubstituted monohydric alcohols having between 1 and 6 [0031] The solubilising agent may be a non-alcoholic solu bilising agent. carbon atoms” is understood to mean compounds having a single hydroxy group and a total of between 1 and 6 carbon [0032] The solubilising agent may be an N-alkyl-pyrroli done such as N-methylpyrrolidone. atoms, Wherein the carbon atoms are not substituted With any [0033] The composition may comprise betWeen about 30% other functional groups. The term excludes monohydric alco (W/W) and about 90% (W/W) of Water. hol compounds having carbon chains interrupted by heteroa [0034] The composition may comprise betWeen about 50% toms, for example oxygen and nitrogen. In one embodiment (W/W) and about 90% (W/W) of Water. of the invention the unsubstituted monohydric alcohol having [0035] The composition may be adapted for topical or between 1 and 6 carbon atoms is ethanol. parenteral administration. In one embodiment, the composi [0054] In the context of the present speci?cation, the term “ tion is a topical composition. or a derivative thereof ’ in relation to pyrrolidone includes [0036] The composition may further comprise one or more pyrrolidone compounds having a Cl-Cl0 alkyl or a Cl-C6 emollients, moisturisers or humectants. alkyl group attached to the nitrogen and/or one or more [0037] The composition may be adapted for gynaecologi Cl-Cl0 alkyl groups or one or more Cl-C6 alkyl groups cal application, for example for application to the vaginal attached to one or more of the carbon atoms of the pyrrolidone epithelial
Load more

Recommended publications
  • Compositions Comprising Drospirenone Molecularly
    (19) & (11) EP 1 748 756 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 9/00 (2006.01) A61K 9/107 (2006.01) 29.04.2009 Bulletin 2009/18 A61K 9/48 (2006.01) A61K 9/16 (2006.01) A61K 9/20 (2006.01) A61K 9/14 (2006.01) (2006.01) (2006.01) (21) Application number: 05708751.2 A61K 9/70 A61K 31/565 (22) Date of filing: 10.03.2005 (86) International application number: PCT/IB2005/000665 (87) International publication number: WO 2005/087194 (22.09.2005 Gazette 2005/38) (54) COMPOSITIONS COMPRISING DROSPIRENONE MOLECULARLY DISPERSED ZUSAMMENSETZUNGEN AUS DROSPIRENON IN MOLEKULARER DISPERSION DES COMPOSITIONS CONTENANT DROSPIRENONE A DISPERSION MOLECULAIRE (84) Designated Contracting States: (72) Inventors: AT BE BG CH CY CZ DE DK EE ES FI FR GB GR • FUNKE, Adrian HU IE IS IT LI LT LU MC NL PL PT RO SE SI SK TR D-14055 Berlin (DE) Designated Extension States: • WAGNER, Torsten AL BA HR MK YU 13127 Berlin (DE) (30) Priority: 10.03.2004 EP 04075713 (74) Representative: Wagner, Kim 10.03.2004 US 551355 P Plougmann & Vingtoft a/s Sundkrogsgade 9 (43) Date of publication of application: P.O. Box 831 07.02.2007 Bulletin 2007/06 2100 Copenhagen Ø (DK) (60) Divisional application: (56) References cited: 08011577.7 / 1 980 242 EP-A- 1 260 225 EP-A- 1 380 301 WO-A-01/52857 WO-A-20/04022065 (73) Proprietor: Bayer Schering Pharma WO-A-20/04041289 US-A- 5 569 652 Aktiengesellschaft US-A- 5 656 622 US-A- 5 789 442 13353 Berlin (DE) Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations.
    [Show full text]
  • The Organic Chemistry of Drug Synthesis
    The Organic Chemistry of Drug Synthesis VOLUME 2 DANIEL LEDNICER Mead Johnson and Company Evansville, Indiana 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 • Chichester • Brisbane • Toronto Copyright © 1980 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 Sections 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: Lednicer, Daniel, 1929- The organic chemistry of drug synthesis. "A Wiley-lnterscience publication." 1. Chemistry, Medical and pharmaceutical. 2. Drugs. 3. Chemistry, Organic. I. Mitscher, Lester A., joint author. II. Title. RS421 .L423 615M 91 76-28387 ISBN 0-471-04392-3 Printed in the United States of America 10 987654321 It is our pleasure again to dedicate a book to our helpmeets: Beryle and Betty. "Has it ever occurred to you that medicinal chemists are just like compulsive gamblers: the next compound will be the real winner." R. L. Clark at the 16th National Medicinal Chemistry Symposium, June, 1978. vii Preface The reception accorded "Organic Chemistry of Drug Synthesis11 seems to us to indicate widespread interest in the organic chemistry involved in the search for new pharmaceutical agents. We are only too aware of the fact that the book deals with a limited segment of the field; the earlier volume cannot be considered either comprehensive or completely up to date.
    [Show full text]
  • Drug Insight: Eplerenone, a Mineralocorticoid- Receptor Antagonist Frances Mcmanus, Gordon T Mcinnes and John MC Connell*
    REVIEW www.nature.com/clinicalpractice/endmet Drug Insight: eplerenone, a mineralocorticoid- receptor antagonist Frances McManus, Gordon T McInnes and John MC Connell* SUMMARY INTRODUCTION The traditional perception of aldosterone as a Increasing recognition of the role of aldosterone in cardiovascular disease hormone of the adrenal zona glomerulosa with has been supported by a significant body of evidence from animal models. actions limited to sodium and water homeostasis This evidence has been translated into clinical practice, and large-scale, is now recognized as incomplete. Nonclassical randomized, placebo-controlled trials have confirmed the beneficial effects of mineralocorticoid blockade in patients with heart failure. As a actions of aldosterone in a variety of nonepithelial target tissues have been demonstrated;1 rapid, consequence, there has been a resurgence in the use of mineralocorticoid- 2 receptor antagonists in clinical practice that has prompted the search nongenomic effects have been identified, and the possibility of local renin–angiotensin–aldosterone for a potent and specific antagonist without the sexual side effects of 3 spironolactone. Eplerenone, a mineralocorticoid-receptor antagonist systems (RAAS) has been suggested. Increasing with minimal binding to the progesterone and androgen receptors, is recognition of aldosterone as a key cardiovascular now licensed for treatment of heart failure in Europe and heart failure hormone has provoked interest in the therapeutic and hypertension in the US; it has also been proposed as a treatment for use of mineralocorticoid-receptor antagonism in a variety of cardiovascular conditions. This article reviews the current a variety of clinical presentations. The adverse- concepts of the actions of aldosterone at a cellular level.
    [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]
  • Autacoids Introduction
    AUTACOIDS INTRODUCTION • AUTACOIDS auto=self akos=healing/remedy • Local Hormones CLASSIFICATION • Amine derived: Histamine (amino acid: Histidine), Serotonin (Tryptophan) • Peptide derived: Angiotensin, Bradykinin • Lipid derived: Prostaglandins, Leukotrienes, Interleukins, Platelet Activating Factor, etc. FUNCTIONS • Physiological • Pathophysiological (Reaction to injuries) • Transmission and Modulation AMINE AUTACOIDS • DERIVED FROM NATURAL AMINO ACIDS • HISTAMINE AND SEROTONIN are the major autacoids in this class HISTAMINE NH2 5 4 1 3 N N H 2 Histamine INTRODUCTION • Imidazole ethylamine • Formed from the amino acid Histidine • Important inflammatory mediator • Potent biogenic amine and plays an important role in inflammation, anaphylaxis, allergies, gastric acid secretion and drug reaction • As part of an immune response to foreign pathogens, its produced by Basophils and mast cells found in nearby connective tissues. SITES OF HISTAMINE RELEASE 1) Mast cell site: Pulmonary tissue (mucosa of bronchial tree) • Skin • GIT(intestinal mucosa) • Conc. Of histamine is particularly high in these tissues 2) Non-mast cell sites: • CNS (neurons) • Epidermis of skin. • GIT(gastric cells) • Cells in regenerating or rapidly growing tissues • Basophils (in the blood) MECHANISM OF RELEASE • Histamine held by an acidic protein and heparin within intracellular granules → Granules extrude by exocytosis → Na+ gets exchanged for histamine • Substances released during IgG or lgM immunoreactions release histamine from the mast cells & basophil. • Chemical
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2004/0058896 A1 Dietrich Et Al
    US 200400.58896A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2004/0058896 A1 Dietrich et al. (43) Pub. Date: Mar. 25, 2004 (54) PHARMACEUTICAL PREPARATION (30) Foreign Application Priority Data COMPRISING AN ACTIVE DISPERSED ON A MATRIX Dec. 7, 2000 (EP)........................................ OO126847.3 (76) Inventors: Rango Dietrich, Konstanz (DE); Publication Classification Rudolf Linder, Kontanz (DE); Hartmut Ney, Konstanz (DE) (51) Int. Cl." ...................... A61K 31156; A61K 31/4439 (52) U.S. Cl. ........................... 514/171; 514/179; 514/338 Correspondence Address: (57) ABSTRACT NATH & ASSOCATES PLLC 1030 FIFTEENTH STREET, N.W. The present invention relates to the field of pharmaceutical SIXTH FLOOR technology and describes a novel advantageous preparation WASHINGTON, DC 20005 (US) for an active ingredient. The novel preparation is Suitable for 9 producing a large number of pharmaceutical dosage forms. (21) Appl. No.: 10/433,398 In the new preparation an active ingredient is present essentially uniformly dispersed in an excipient matrix com (22) PCT Filed: Dec. 6, 2001 posed of one or more excipients Selected from the group of fatty alcohol, triglyceride, partial glyceride and fatty acid (86) PCT No.: PCT/EPO1/14307 eSter. US 2004/0058896 A1 Mar. 25, 2004 PHARMACEUTICAL PREPARATION 0008 Further subject matters are evident from the claims. COMPRISING AN ACTIVE DISPERSED ON A MATRIX 0009. The preparations for the purpose of the invention preferably comprise numerous individual units in which at least one active ingredient particle, preferably a large num TECHNICAL FIELD ber of active ingredient particles, is present in an excipient 0001. The present invention relates to the field of phar matrix composed of the excipients of the invention (also maceutical technology and describes a novel advantageous referred to as active ingredient units hereinafter).
    [Show full text]
  • EVIDENCE of GENE EXPRESSION and ENZYME ACTIVITY By
    STEROID HYDROXYLASES IN THE RAT BRAIN: EVIDENCE OF GENE EXPRESSION AND ENZYME ACTIVITY by SCOTT M. MacKENZIE B.Sc.(Hons) © Scott M. MacKenzie, March 2000 Thesis submitted for the degree of Doctor of Philosophy to the University of Glasgow Department of Medicine and Therapeutics UNIVERSITY OF GLASGOW Western Infirmary, Glasgow 1 ProQuest Number: 11007810 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 11007810 Published by ProQuest LLC(2018). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 G IA SG O W UNIVERSITY LIBRARY , liW ^ Abstract Aldosterone and corticosterone are the main mineralocorticoid and glucocorticoid products of the rat adrenal cortex. They share a common biosynthetic pathway until the final stage where the substrate deoxycorticosterone (DOC) is converted to either aldosterone or corticosterone by the actions of the enzymes aldosterone synthase (CYP11B2) or llp-hydroxylase (CYP11B1) respectively. These enzymes are the products of highly homologous genes whose expression, along with that of other components of the corticosteroidogenic pathway, was long thought to be confined to the adrenal cortex. In recent years, however, due to the advent of more sensitive molecular biological techniques, evidence has accumulated to suggest that this is not the case and that certain extra-adrenal tissues may be capable of autonomous aldosterone and corticosterone production.
    [Show full text]
  • A Computational Study of the Substrate Conversion and Selective Inhibition of Aldosterone Synthase
    A computational study of the substrate conversion and selective inhibition of aldosterone synthase Citation for published version (APA): Roumen, L. (2008). A computational study of the substrate conversion and selective inhibition of aldosterone synthase. Technische Universiteit Eindhoven. https://doi.org/10.6100/IR637195 DOI: 10.6100/IR637195 Document status and date: Published: 01/01/2008 Document Version: Publisher’s PDF, also known as Version of Record (includes final page, issue and volume numbers) Please check the document version of this publication: • A submitted manuscript is the version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal.
    [Show full text]
  • European Patent Office of Opposition to That Patent, in Accordance with the Implementing Regulations
    (19) & (11) EP 1 748 756 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 9/00 (2006.01) A61K 9/107 (2006.01) 29.04.2009 Bulletin 2009/18 A61K 9/48 (2006.01) A61K 9/16 (2006.01) A61K 9/20 (2006.01) A61K 9/14 (2006.01) (2006.01) (2006.01) (21) Application number: 05708751.2 A61K 9/70 A61K 31/565 (22) Date of filing: 10.03.2005 (86) International application number: PCT/IB2005/000665 (87) International publication number: WO 2005/087194 (22.09.2005 Gazette 2005/38) (54) COMPOSITIONS COMPRISING DROSPIRENONE MOLECULARLY DISPERSED ZUSAMMENSETZUNGEN AUS DROSPIRENON IN MOLEKULARER DISPERSION DES COMPOSITIONS CONTENANT DROSPIRENONE A DISPERSION MOLECULAIRE (84) Designated Contracting States: (72) Inventors: AT BE BG CH CY CZ DE DK EE ES FI FR GB GR • FUNKE, Adrian HU IE IS IT LI LT LU MC NL PL PT RO SE SI SK TR D-14055 Berlin (DE) Designated Extension States: • WAGNER, Torsten AL BA HR MK YU 13127 Berlin (DE) (30) Priority: 10.03.2004 EP 04075713 (74) Representative: Wagner, Kim 10.03.2004 US 551355 P Plougmann & Vingtoft a/s Sundkrogsgade 9 (43) Date of publication of application: P.O. Box 831 07.02.2007 Bulletin 2007/06 2100 Copenhagen Ø (DK) (60) Divisional application: (56) References cited: 08011577.7 / 1 980 242 EP-A- 1 260 225 EP-A- 1 380 301 WO-A-01/52857 WO-A-20/04022065 (73) Proprietor: Bayer Schering Pharma WO-A-20/04041289 US-A- 5 569 652 Aktiengesellschaft US-A- 5 656 622 US-A- 5 789 442 13353 Berlin (DE) Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations.
    [Show full text]
  • STARLING REVIEW the New Biology of Aldosterone
    1 STARLING REVIEW The new biology of aldosterone .. John M C Connell and Eleanor Davies MRC Blood Pressure Group, Division of Cardiovascular and Medical Sciences, University of Glasgow, Gardiner Institute, Western Infirmary, Glasgow G11 6NT, UK (Requests for offprints should be addressed to J M C Connell; Email: [email protected]) Abstract Classically, aldosterone is synthesised in the adrenal zona principal source of circulating and locally available glomerulosa and binds to specific mineralocorticoid hormone. receptors located in the cytosol of target epithelial cells. Recent studies have shown major therapeutic benefits of Translocation of the resulting steroid receptor complex to mineralocorticoid receptor antagonism in cardiac failure, the cell nucleus modulates gene expression and translation which emphasise the importance of aldosterone in caus- of specific ‘aldosterone-induced’ proteins that regulate ing adverse cardiovascular pathophysiological effects. electrolyte and fluid balance. However, non-epithelial Additional evidence demonstrates that aldosterone levels and rapid non-genomic actions of aldosterone have also predict development of high blood pressure in normo- been described that account for a variety of actions of tensive subjects, while it is now clear that increased aldosterone that contribute to blood pressure homeostasis. aldosterone action contributes to hypertension and cardio- These include key actions on endothelial cells and on vascular damage in approximately 10% of patients with cardiac tissue. established hypertension. There is also evidence that aldosterone can be syn- These new findings highlight the role of aldosterone as thesised in other tissues; the most convincing evidence a key cardiovascular hormone and extend our understand- relates to the central nervous system.
    [Show full text]
  • Molecular Evolution of the Switch for Progesterone and Spironolactone from Mineralocorticoid Receptor Agonist to Antagonist
    Molecular evolution of the switch for progesterone and spironolactone from mineralocorticoid receptor agonist to antagonist Peter J. Fullera,b,1, Yi-Zhou Yaoa,b, Ruitao Jinc, Sitong Hec, Beatriz Martín-Fernándeza,b,2, Morag J. Younga,b, and Brian J. Smithc aCentre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, VIC 3168, Australia; bDepartment of Molecular Translational Science, Monash University, Clayton, VIC 3168, Australia; and cLa Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia Edited by Huda Akil, University of Michigan, Ann Arbor, MI, and approved July 29, 2019 (received for review February 25, 2019) The mineralocorticoid receptor (MR) is highly conserved across In the present study, we demonstrate that a single residue change vertebrate evolution. In terrestrial vertebrates, the MR mediates is responsible for the switch from an agonist response to progesterone sodium homeostasis by aldosterone and also acts as a receptor for for zebrafish MR (zMR) to antagonist for human MR (hMR). This cortisol. Although the MR is present in fish, they lack aldosterone. change in the MR ligand-binding domain (LBD) is surprisingly dis- The MR binds progesterone and spironolactone as antagonists in tant from the ligand-binding site and has not previously been asso- human MR but as agonists in zebrafish MR. We have defined the ciated with agonist to antagonist switching in the MR. molecular basis of these divergent responses using MR chimeras between the zebrafish and human MR coupled with reciprocal Results site-directed mutagenesis and molecular dynamic (MD) simulation LBD Mediates the Agonist Response of the Zebrafish MR to based on the crystal structures of the MR ligand-binding domain.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,715,735 B2 Funke Et Al
    US008715735B2 (12) United States Patent (10) Patent No.: US 8,715,735 B2 Funke et al. (45) Date of Patent: May 6, 2014 (54) STABILISED SUPERSATURATED SOLIDS OF OTHER PUBLICATIONS LIPOPHILIC DRUGS V. Buehler, “Kollidon (R). Polyvinylpyrrollidone for the pharmaceu (75) Inventors: Adrian Funke, Berlin (DE); Torsten tical industry.” Mar. 1998, BASF AG Fine Chemicals, Ludwigshafen, Wagner, Berlin (DE); Ralph Lipp, Germany, pp. 88-116, XP002297940. Zionsville, IN (US) K. Khougaz et al., “Crystallization inhibition in solid dispersions of (73) Assignee: Bayer Intellectual Property GmbH, MK-0591 and poly(vinylpyrrollidone)polymers,” Journal of Pharma Monehim (DE) ceutical Sciences, Oct. 2000, vol. 89, No. 10, pp. 1325-1334. XP002297939, the whole document. (*) Notice: Subject to any disclaimer, the term of this T. Watanabe et al., "Stability of amorphous indomethacin com patent is extended or adjusted under 35 pounded with silica.” International Journal of Pharmaceutics, U.S.C. 154(b) by 759 days. 2001, vol. 226, pp. 81-91, XP002310637. (21) Appl. No.: 11/076,022 T. Watanabe et al., “Prediction of apparent equilibrium solubility of indomethacin compounded with silica by 13C solid state NMR.” Int. (22) Filed: Mar 10, 2005 J. Pharmaceutics, 2002, vol. 248, pp. 123-129, XP002310638. (65) Prior Publication Data T. Watanabe et al., “Comparison between polyvinylpyrrollidone and silica nanoparticles as carriers for indomethacin in a solid state dis US 2005/02O7990 A1 Sep. 22, 2005 persion.” Int. J. Pharmaceutics, 2003, vol. 250, pp. 283-286, XPOO23 10639. Related U.S. Application Data H. Takeuchi et al., “Spherical Solid dispersion containing amorphous tolbutamide embedded in enteric coating polymers or colloidal silica (60) Provisional application No.
    [Show full text]