DOCSLIB.ORG

X 4,182,330 11) 4,182,330 Michaels 45) Jan

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
X 4,182,330 11) 4,182,330 Michaels 45) Jan 424 - 450 SR C8 (73. x 4,182,330 11) 4,182,330 Michaels 45) Jan. 8, 1980 (54). AMPHIPATHICMEANS FOR ADMINISTERING MEDICAMENT OTHER PUBLICATIONS 75) Inventor: Alan S. Michaels, Atherton, Calif. The Pharmacological Basis of Therapeutics, 1970, 4th Ed., pp. 677-708. 73) Assignee: Alza Corporation, Palo Alto, Calif. Pharmaceutical Sciences, 1970, 14th Ed., pp. 858-864. 21 Appl. No.: 818,292 Primary Examiner-Robert W. Michell (22 Filed: Jul. 25, 1977 Assistant Examiner-C. F. Rosenbaum . Attorney, Agent, or Firm-Paul L. Sabatine; Thomas E. 51 int. C.’............................................. A61M 37/00 Ciotti; Edward L. Mandell 52 U.S. Cl. ....................................... 128/260; 424/15 58) Field of Search ................................ 128/260-268, 57 ABSTRACT 128/222; 424/15 Means for administering an amphipathic medicament by 56) References Cited micelle solubilization is disclosed. The nicelle consists U.S. PATENT DOCUMENTS of a nonionic surfactant medicament adduct. The ad duct is coated onto an osmotically effective solute and 3,845,770 il/1974 Theeuves et al..................... 128/260 housed in al osmotic therapeutic system for administer 3,926, 88 12/1975 Baker et al. .......................... 128/260 ing the medicament in a therapeutically effective 3,952,741 4/1976 Baker ................................... 128/260 4,008,719 2/1977. Theeuves et al. .................... 7 amount over a prolonged period of time. 404,334 3/1977 Theeuves et al. ... 28/260 4,036,227 7/977 Zaffaroni et al. ..... ... 128/260 9 Claims, 2 Drawing Figures U.S. Patent Jan. 8, 1980 4,182,330 4,182,330 1. 2 ble by an osmotic therapeutic system over a prolonged MEANS FOR ADMINISTERING AMPHPATHC period of time. MEDCAMENT Another object of the invention is to provide a phar maceutical formulation useful for administering digital FIELD OF THE INVENTION oid drugs in a controlled and continuous manner over a The present invention pertains to an osmotic dosage prolonged period of time. formulation useful for administering amphipathic medi A further object of the invention is to provide an Carments. osmotic dosage form useful for dispensing cardiac glycosides for the treatment of cardiac decompensation. BACKGROUND OF THE INVENTION 10 Yet a further object of the invention is to provide an oral osniotic therapeutic system useful for administering Many valuable medicaments widely used by the med digitaloid drugs to a warm-blooded animal including ical and veterinary professions are known to possess humans at a controlled and continuous rate over a pro amphipathic properties. This property, of solvent longed period of time. attracting and solvent-repelling within a single medica 15 Other objects and advantages of the present invention ment, severely restricts both the medicament's formula will become more apparent from the following detailed tion into operable dosage forms and its administration in description of the invention and the appended claims a controlled and continuous manner for obtaining its defining the scope thereof. beneficial effects. For example, one valuable class of medicaments exhibiting nonionic amphipathic proper 20 SUMMARY OF THE INVENTION ties are cardiac acting digitaloid drugs. These drugs The invention concerns a pharmaceutical formula have as their major pharmacological action the ability tion comprising an amphipathic drug such as a cardiac to effect cardiovascular functions and they are there glycoside drug, capable of administration over a pro fore widely used for tile management of heart condi longed period of time. The formulation comprises a tions. The drugs are used to improve heart muscle activ 25 micellar aggregate consisting of a drug/nonionic surfac ity and tone, and for treating congestive heart failure. tant adduct, which adduct is coated onto an osmotically The digitaloid drugs commonly used for the present effective solute. The formulation is charged into an oral purpose are often referred to as cardiac glycosides. osmotic system and the drug is dispensed therefrom. While these drugs possess beneficial properties, their amphipathic properties are shortcomings associated 30 DETALED DESCRIPTION OF THE with their use. For example, drugs such as digoxin, the DISCLOSURE cardiotonic glycoside obtained from Digitalis lanata, In accordance with the practice of the present inven and with digitoxin, the cardiotonic glycoside from Digi tion, it has now been found that amphipathic drugs can talis purpurea, their insolubility in water and their lim be compounded into a formulation capable of adminis ifed solubility in organic carriers restricts manufactur 35 tration from an osmotic therapeutic system into a pre ing the drugs into formulations suitable for administer dominantly aqueous, biological environment. The for ing them in a controlled and continuous manner. The mulation consists essentially of a micellar aggregate of prior art attempted to improve on their administration (1) the drug, and (2) a nonionic surfactant forming an by mixing the drugs with cocoa-butter, solidified glyc adduct, which adduct is 3) coated onto an osmotically erine and paraffin wax, but this has not lead to true effective solute. The formulation is charged into the controlled formulations. See The Pharmacological Basis compartment of an oral osmotic therapeutic system. of Therapeutics, by Goodman and Gilman, 4th Ed., The system comprises a semipermeable wall surround pages 677 to 708, 1970, published by the MacMillian ing the compartment with a passageway through the Company, New York; and Pharmaceutical Sciences by wall for releasing drug therefrom. Remington, 14th Ed., pages 858 to 864, 1970, published 45 Exemplary drugs or medicaments that can be admin by Mack Publishing Company, Easton, Pennsylvania. It istgged according to the spirit of the invention include will be appreciated by those versed in the present art, locally and systemically acting drugs. These include a that in view of the above presentation, a critical need member selected from the group consisting of physio exists for a means for administering amphipathic drugs, logically and pharmacologically effective drugs, such as 50 central nervous system acting drugs, hypnotic, sedative, and if such were made available it would represent a psychic energizer, tranquilizer, anticonvulsant, antipar valuable and useful contribution to the practicing art. kinson, muscle relaxant, analgesic, antipyretic, anti-in OBJ ECTs, OF THE INVENTION flammatory, anesthetic, antispasmodic, antimicrobial, antiviral, antiulcer, hormonal, sympathomimetic, di Accordingly, it is an immediate object of this inven 55 uretic, hypoglycemic, vitamin and ophthalmic drugs. tion to provide a novel and useful means for administer The beneficial drugs and the dose amount for humans ing amphipathic medicaments which means overcomes are known to the art in Remington's Pharmaceutical the shortcomings associaied with the prior art. Sciences, 14th Ed., 1970, published by Mack Publishing Another immediate object of the invention is to pro Co., Easton, Penna., in The Pharmacological Basis of vide a dosage form that can administer in a controlled 60 Therapeutics, by Goudman and Gilman, 4th Ed., 1970, and continuous manner medicaments possessing both published by the MacMillian Co., London, and in U.S. hydrophilic and hydrophobic properties. Pat. No. 3,977,404, which patent is assigned to the A further object of this invention is to provide an ALZA Corp. of Palo Alto, Calif., the assignee of this osmotic dosage form useful for dispensing amphiphilic patent application. medicaments for the treatment of their intended effects. 65 A presently preferred class of drugs that can be ad Still a further object of the invention is to administer ministered according to the mode and manner of this drug by micellar solubilization which micelle consists of invention are the digitaloid or cardiac glycoside drugs. a amphipathic drug/nonionic adduct and is administra The digitaloid or cardiac glycoside drugs that can be ... 4,182,330 3 i 4. administered are the drugs characterized by the highly Exemplary osmotically effective solutes suitable for specific and powerful action which they exert upon the receiving a coating of the adduct on their surface in cardiac muscle. These drugs are valuable in the treat clude solutes that exhibit an osmotic pressure gratient ment of congestive heart failure due to heart disease or across the semipermeable wall of an osmotic device other causes. The drugs stimulate the heart to greater against an external fluid. Solutes capable of imbibing contractile activity and they restore the original tonic external fluid into the compartment include magnesium ity. In physiological and pharmacological operations, sulfate, magnesium chloride, sodium chloride, lithium the ventricles are more completely emptied, blood flow chloride, potassium sulfate, sodium carbonate, sodium is increased in the heart, heart muscle nourishment is sulfate, lithium bicarbonate, sodium sulfate, calcium increased and becomes more efficient and heart size is O sulfate, calcium lactate, mannitol, urea, inositol, magne decreased. sium succinate, raffinose, sucrose, gluctose and lactose. Exemplary cardiac glycoside for the present purpose Generally, a 1.0 to 1000 m (micrometers) layer of include digitoxigenin; digitoxigenin-g-D-glucoside; dig drug/surfactant adduct is coated onto the exposed sur itoxin; digitoxigenin-g-tetracetyl-D-glucoside; acetyl face of the osmotically effective solute particles, to form digitoxin; desacetyldigilanide,
Load more

Recommended publications
  • Combination of Pretreatments with Acetic Acid and Sodium Methoxide for Efficient Digoxin Preparation from Digitalis Glycosides in Digitalis Lanata Leaves
    Pharmacology & Pharmacy, 2016, 7, 200-207 Published Online May 2016 in SciRes. http://www.scirp.org/journal/pp http://dx.doi.org/10.4236/pp.2016.75026 Combination of Pretreatments with Acetic Acid and Sodium Methoxide for Efficient Digoxin Preparation from Digitalis Glycosides in Digitalis lanata Leaves Yasuhiko Higashi*, Yukari Ikeda, Youichi Fujii Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan Received 21 April 2016; accepted 28 May 2016; published 31 May 2016 Copyright © 2016 by authors and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/ Abstract We previously developed an HPLC method for determination of lanatoside C, digoxin and α-acetyl- digoxin in digitalis glycosides isolated from Digitalis lanata leaves. Here, we present an improved HPLC-UV method to determine those compounds and deslanoside. We used the improved method to examine the effects of various pretreatments on the amounts of the four compounds isolated from the leaves, with the aim of maximizing the yield of digoxin. Leaves were extracted with 50% methanol, followed by clean-up on a Sep-Pak C18 cartridge prior to HPLC analysis. The amounts of lanatoside C, digoxin and α-acetyldigoxin per 100 mg of the leaves without pretreatment were 115.6, 7.45 and 23.8 μg, respectively (deslanoside was not detected). Pretreatment with acetic ac- id, which activated deglucosylation mediated by digilanidase present in the leaves, increased the amounts of digoxin and α-acetyldigoxin, while lanatoside C and deslanoside were not detected. Pretreatment with sodium methoxide, which hydrolyzed lanatoside C to deslanoside, increased the yields of deslanoside and digoxin, while lanatoside C and α-acetyldigoxin were not detected.
    [Show full text]
  • Chemistry, Spectroscopic Characteristics and Biological Activity of Natural Occurring Cardiac Glycosides
    IOSR Journal of Biotechnology and Biochemistry (IOSR-JBB) ISSN: 2455-264X, Volume 2, Issue 6 Part: II (Sep. – Oct. 2016), PP 20-35 www.iosrjournals.org Chemistry, spectroscopic characteristics and biological activity of natural occurring cardiac glycosides Marzough Aziz DagerAlbalawi1* 1 Department of Chemistry, University college- Alwajh, University of Tabuk, Saudi Arabia Abstract:Cardiac glycosides are organic compounds containing two types namely Cardenolide and Bufadienolide. Cardiac glycosides are found in a diverse group of plants including Digitalis purpurea and Digitalis lanata (foxgloves), Nerium oleander (oleander),Thevetiaperuviana (yellow oleander), Convallariamajalis (lily of the valley), Urgineamaritima and Urgineaindica (squill), Strophanthusgratus (ouabain),Apocynumcannabinum (dogbane), and Cheiranthuscheiri (wallflower). In addition, the venom gland of cane toad (Bufomarinus) contains large quantities of a purported aphrodisiac substance that has resulted in cardiac glycoside poisoning.Therapeutic use of herbal cardiac glycosides continues to be a source of toxicity today. Recently, D.lanata was mistakenly substituted for plantain in herbal products marketed to cleanse the bowel; human toxicity resulted. Cardiac glycosides have been also found in Asian herbal products and have been a source of human toxicity.The most important use of Cardiac glycosides is its affects in treatment of cardiac failure and anticancer agent for several types of cancer. The therapeutic benefits of digitalis were first described by William Withering in 1785. Initially, digitalis was used to treat dropsy, which is an old term for edema. Subsequent investigations found that digitalis was most useful for edema that was caused by a weakened heart. Digitalis compounds have historically been used in the treatment of chronic heart failure owing to their cardiotonic effect.
    [Show full text]
  • Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set
    MTC eHealth DSI [eHDSI v2.2.2-OR] eHealth DSI – Master Value Set Catalogue Responsible : eHDSI Solution Provider PublishDate : Wed Nov 08 16:16:10 CET 2017 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 1 of 490 MTC Table of Contents epSOSActiveIngredient 4 epSOSAdministrativeGender 148 epSOSAdverseEventType 149 epSOSAllergenNoDrugs 150 epSOSBloodGroup 155 epSOSBloodPressure 156 epSOSCodeNoMedication 157 epSOSCodeProb 158 epSOSConfidentiality 159 epSOSCountry 160 epSOSDisplayLabel 167 epSOSDocumentCode 170 epSOSDoseForm 171 epSOSHealthcareProfessionalRoles 184 epSOSIllnessesandDisorders 186 epSOSLanguage 448 epSOSMedicalDevices 458 epSOSNullFavor 461 epSOSPackage 462 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 2 of 490 MTC epSOSPersonalRelationship 464 epSOSPregnancyInformation 466 epSOSProcedures 467 epSOSReactionAllergy 470 epSOSResolutionOutcome 472 epSOSRoleClass 473 epSOSRouteofAdministration 474 epSOSSections 477 epSOSSeverity 478 epSOSSocialHistory 479 epSOSStatusCode 480 epSOSSubstitutionCode 481 epSOSTelecomAddress 482 epSOSTimingEvent 483 epSOSUnits 484 epSOSUnknownInformation 487 epSOSVaccine 488 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 3 of 490 MTC epSOSActiveIngredient epSOSActiveIngredient Value Set ID 1.3.6.1.4.1.12559.11.10.1.3.1.42.24 TRANSLATIONS Code System ID Code System Version Concept Code Description (FSN) 2.16.840.1.113883.6.73 2017-01 A ALIMENTARY TRACT AND METABOLISM 2.16.840.1.113883.6.73 2017-01
    [Show full text]
  • Pharmacokinetics, Bioavailability and Serum Levels of Cardiac Glycosides
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE JACCVol. 5, No.5 provided by Elsevier - Publisher43A Connector May 1985:43A-50A Pharmacokinetics, Bioavailability and Serum Levels of Cardiac Glycosides THOMAS W. SMITH, MD, FACC Boston. Massachusetts Digoxin, the cardiac glycoside most frequently used in bioavailability of digoxin is appreciably less than that of clinical practice in the United States, can be givenorally digitoxin, averaging about two-thirds to three-fourths of or intravenously and has an excretory half-life of 36 to the equivalent dose given intravenously in the case of 48 hours in patients with serum creatinine and blood currently available tablet formulations. Recent studies urea nitrogen values in the normal range. Sincethe drug have shown that gut ftora of about 10% of patients re­ is excreted predominantly by the kidney, the half-life is duce digoxin to a less bioactive dihydro derivative. This prolonged progressivelywithdiminishingrenal function, process is sensitiveto antibiotic administration, creating reaching about 5 days on average in patients who are the potential for important interactions among drugs. essentially anephric. Serum protein binding of digoxin Serum or plasma concentrations of digitalis glycosides is only about 20%, and differs markedly in this regard can be measured by radioimmunoassay methods that are from that of digitoxin, which is 97% bound by serum nowwidelyavailable, but knowledgeofserum levelsdoes albumin at usual therapeutic levels. Digitoxin is nearly not substitute for a sound working knowledge of the completely absorbed from the normal gastrointestinal clinical pharmacology of the preparation used and care­ tract and has a half-lifeaveraging 5 to 6 days in patients ful patient follow-up.
    [Show full text]
  • Pharmaceutical Appendix to the Tariff Schedule 2
    Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. ABACAVIR 136470-78-5 ACIDUM LIDADRONICUM 63132-38-7 ABAFUNGIN 129639-79-8 ACIDUM SALCAPROZICUM 183990-46-7 ABAMECTIN 65195-55-3 ACIDUM SALCLOBUZICUM 387825-03-8 ABANOQUIL 90402-40-7 ACIFRAN 72420-38-3 ABAPERIDONUM 183849-43-6 ACIPIMOX 51037-30-0 ABARELIX 183552-38-7 ACITAZANOLAST 114607-46-4 ABATACEPTUM 332348-12-6 ACITEMATE 101197-99-3 ABCIXIMAB 143653-53-6 ACITRETIN 55079-83-9 ABECARNIL 111841-85-1 ACIVICIN 42228-92-2 ABETIMUSUM 167362-48-3 ACLANTATE 39633-62-0 ABIRATERONE 154229-19-3 ACLARUBICIN 57576-44-0 ABITESARTAN 137882-98-5 ACLATONIUM NAPADISILATE 55077-30-0 ABLUKAST 96566-25-5 ACODAZOLE 79152-85-5 ABRINEURINUM 178535-93-8 ACOLBIFENUM 182167-02-8 ABUNIDAZOLE 91017-58-2 ACONIAZIDE 13410-86-1 ACADESINE 2627-69-2 ACOTIAMIDUM 185106-16-5 ACAMPROSATE 77337-76-9
    [Show full text]
  • Multidose Evaluation of 6,710 Drug Repurposing Library Identifies Potent SARS-Cov-2 Infection Inhibitors in Vitro and in Vivo
    bioRxiv preprint doi: https://doi.org/10.1101/2021.04.20.440626; this version posted April 22, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Multidose evaluation of 6,710 drug repurposing library identifies potent SARS-CoV-2 infection inhibitors In Vitro and In Vivo. JJ Patten1, P. T. Keiser 1, D. Gysi2,3, G. Menichetti 2,3, H. Mori 1, C. J. Donahue 1, X. Gan 2,3, I. Do Valle 2, , K. Geoghegan-Barek 1, M. Anantpadma 1,4, J. L. Berrigan 1, S. Jalloh1, T. Ayazika1, F. Wagner6, M. Zitnik 2, S. Ayehunie6, D. Anderson1, J. Loscalzo3, S. Gummuluru1, M. N. Namchuk7, A. L. Barabasi2,3,8, and R. A. Davey1. Addresses: 1. Department of Microbiology, Boston University School of Medicine and NEIDL, Boston University, Boston, MA, 02118, USA. 2. Center for Complex Network Research, Northeastern University, Boston, Massachusetts 02115, USA. 3. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. 4. present address: Analytical Development, WuXi Advanced Therapies, Philadelphia, PA, 19112, USA. 5. Center for the Development of Therapeutics, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA. 6. MatTek Corporation, Ashland, MA 01721, USA. 7. Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA. 02115, USA. 8. Department of Network and Data Science, Central European University, Budapest 1051, Hungary. Abstract The SARS-CoV-2 pandemic has caused widespread illness, loss of life, and socioeconomic disruption that is unlikely to resolve until vaccines are widely adopted, and effective therapeutic treatments become established.
    [Show full text]
  • Marrakesh Agreement Establishing the World Trade Organization
    No. 31874 Multilateral Marrakesh Agreement establishing the World Trade Organ ization (with final act, annexes and protocol). Concluded at Marrakesh on 15 April 1994 Authentic texts: English, French and Spanish. Registered by the Director-General of the World Trade Organization, acting on behalf of the Parties, on 1 June 1995. Multilat ral Accord de Marrakech instituant l©Organisation mondiale du commerce (avec acte final, annexes et protocole). Conclu Marrakech le 15 avril 1994 Textes authentiques : anglais, français et espagnol. Enregistré par le Directeur général de l'Organisation mondiale du com merce, agissant au nom des Parties, le 1er juin 1995. Vol. 1867, 1-31874 4_________United Nations — Treaty Series • Nations Unies — Recueil des Traités 1995 Table of contents Table des matières Indice [Volume 1867] FINAL ACT EMBODYING THE RESULTS OF THE URUGUAY ROUND OF MULTILATERAL TRADE NEGOTIATIONS ACTE FINAL REPRENANT LES RESULTATS DES NEGOCIATIONS COMMERCIALES MULTILATERALES DU CYCLE D©URUGUAY ACTA FINAL EN QUE SE INCORPOR N LOS RESULTADOS DE LA RONDA URUGUAY DE NEGOCIACIONES COMERCIALES MULTILATERALES SIGNATURES - SIGNATURES - FIRMAS MINISTERIAL DECISIONS, DECLARATIONS AND UNDERSTANDING DECISIONS, DECLARATIONS ET MEMORANDUM D©ACCORD MINISTERIELS DECISIONES, DECLARACIONES Y ENTEND MIENTO MINISTERIALES MARRAKESH AGREEMENT ESTABLISHING THE WORLD TRADE ORGANIZATION ACCORD DE MARRAKECH INSTITUANT L©ORGANISATION MONDIALE DU COMMERCE ACUERDO DE MARRAKECH POR EL QUE SE ESTABLECE LA ORGANIZACI N MUND1AL DEL COMERCIO ANNEX 1 ANNEXE 1 ANEXO 1 ANNEX
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2009/0246185 A1 Kishida Et Al
    US 20090246185A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0246185 A1 Kishida et al. (43) Pub. Date: Oct. 1, 2009 (54) CARDIAC DYSFUNCTION-AMELIORATING (30) Foreign Application Priority Data AGENT OR CARDAC FUNCTION-MANTAININGAGENT Mar. 13, 2006 (JP) ................................. 2006-066992 Nov. 21, 2006 (JP) ................................. 2006-314034 (75) Inventors: Hideyuki Kishida, Hyogo (JP); O O Kenji Fujii, Hyogo (JP); Hiroshi Publication Classification Kubo, Hyogo (JP); Kazunori (51) Int. Cl. Hosoe, Hyogo (JP) A6II 3L/22 (2006.01) CD7C 43/23 (2006.01) Correspondence Address: A6IP 9/00 (2006.01) SUGHRUE MION, PLLC (52) U.S. Cl. ........................................ 424/94.1:568/651 2100 PENNSYLVANIA AVENUE, N.W., SUITE 8OO (57) ABSTRACT WASHINGTON, DC 20037 (US) An object of the present invention is to provide a highly safe oral composition Superior in a cardiac dysfunction-amelio (73) Assignee: KANEKA CORPORATION, rating or cardiac function-maintaining action. The present OSAKA-SHI, OSAKA (JP) inventors have conducted intensive studies in an attempt to solve the aforementioned problems and found that use of (21) Appl. No.: 12/282,448 particularly, reduced coenzyme Q10 from among highly safe coenzyme Q affords a composition useful for amelioration of (22) PCT Filed: Mar. 9, 2007 cardiac dysfunction and maintenance of cardiac function. Accordingly, the present invention provides a cardiac dys (86). PCT No.: PCT/UP2007/O54.643 function-ameliorating agent or cardiac function-maintaining agent containing reduced coenzyme Qas an active ingredient, S371 (c)(1), and a pharmaceutical product, a food, an animal drug, a feed (2), (4) Date: Dec. 23, 2008 and the like, which contain the agent.
    [Show full text]
  • Eiichi Kimura, MD, Department of Internal Medicine, Nippon Medical
    Effect of Metildigoxin (ƒÀ-Methyldigoxin) on Congestive Heart Failure as Evaluated by Multiclinical Double Blind Study Eiichi Kimura,* M.D. and Akira SAKUMA,** Ph.D. In Collaboration with Mitsuo Miyahara, M.D. (Sapporo Medi- cal School, Sapporo), Tomohiro Kanazawa, M.D. (Akita Uni- versity School of Medicine, Akita), Masato Hayashi, M.D. (Hiraga General Hospital, Akita), Hirokazu Niitani, M.D. (Showa Uni- versity School of Medicine, Tokyo), Yoshitsugu Nohara, M.D. (Tokyo Medical College, Tokyo), Satoru Murao, M.D. (Faculty of Medicine, University of Tokyo, Tokyo), Kiyoshi Seki, M.D. (Toho University School of Medicine, Tokyo), Michita Kishimoto, M.D. (National Medical Center Hospital, Tokyo), Tsuneaki Sugi- moto, M.D. (Faculty of Medicine, Kanazawa University, Kana- zawa), Masao Takayasu, M.D. (National Kyoto Hospital, Kyoto), Hiroshi Saimyoji, M.D. (Faculty of Medicine, Kyoto University, Kyoto), Yasuharu Nimura, M.D. (Medical School, Osaka Uni- versity, Osaka), Tatsuya Tomomatsu, M.D. (Kobe University, School of Medicine, Kobe), and Junichi Mise, M.D. (Yamaguchi University, School of Medicine, Ube). SUMMARY The efficacy on congestive heart failure of metildigoxin (ƒÀ-methyl- digoxin, MD), a derivative of digoxin (DX), which had a good absorp- tion rate from digestive tract, was examined in a double blind study using a group comparison method. After achieving digitalization with oral MD or intravenous deslanoside in the non-blind manner, mainte- nance treatment was initiated and the effects of orally administered MD and DX were compared. MD was administered in 44 cases , DX in 42. The usefulness of the drug was evaluated after 2 weeks , taking into account the condition of the patient and the ease of administration .
    [Show full text]
  • Cardenolide Biosynthesis in Foxglove1
    Review 491 Cardenolide Biosynthesis in Foxglove1 W. Kreis2,k A. Hensel2, and U. Stuhlemmer2 1 Dedicated to Prof. Dr. Dieter He@ on the occasion of his 65th birthday 2 Friedrich-Alexander-Universität Erlangen, Institut für Botanik und Pharmazeutische Biologie, Erlangen, Germany Received: January 28, 1998; Accepted: March 28, 1998 Abstract: The article reviews the state of knowledge on the genuine cardiac glycosides present in Digitalis species have a biosynthesis of cardenolides in the genus Digitalis. It sum- terminal glucose: these cardenolides have been termed marizes studies with labelled and unlabelled precursors leading primary glycosides. After harvest or during the controlled to the formulation of the putative cardenolide pathway. Alter- fermentation of dried Digitalis leaves most of the primary native pathways of cardenolide biosynthesis are discussed as glycosides are hydrolyzed to yield the so-called secondary well. Special emphasis is laid on enzymes involved in either glycosides. Digitalis cardenolides are valuable drugs in the pregnane metabolism or the modification of cardenolides. medication of patients suffering from cardiac insufficiency. In About 20 enzymes which are probably involved in cardenolide therapy genuine glycosides, such as the lanatosides, are used formation have been described "downstream" of cholesterol, as well as compounds obtained after enzymatic hydrolysis including various reductases, oxido-reductases, glycosyl trans- and chemical saponification, for example digitoxin (31) and ferases and glycosidases as well as acyl transferases, acyl es- digoxin, or chemical modification of digoxin, such as metildig- terases and P450 enzymes. Evidence is accumulating that car- oxin. Digitalis lanata Ehrh. and D.purpurea L are the major denolides are not assembled on one straight conveyor belt but sources of the cardiac glycosides most frequently employed in instead are formed via a complex multidimensional metabolic medicine.
    [Show full text]
  • Radioimmunoassay
    Radioimmunoassay Measurement of Serum Cardiac Glycoside Levels: Using Pharmacologic Principles to Solve Crossreactivity Problems Thomas J. Persoon The University of Iowa, Iowa City, Iowa Laboratories performing analyses for serum cardiac Results glycosides are sometimes faced with the problem of dis­ Data collected in our laboratory are similar to those tinguishing between digoxin and digitoxin in a specimen. published by Kuno-Sakai. Tables 3 and 4 show the The antibodies to the cardiac glycosides supplied with measured concentrations of digoxin and digitoxin from radioimmunoassay kits for these drugs have some patient sera known to contain only one drug. Figure 1 measurable degree of cross reactivity. Therapeutic levels is a plot of measured digoxin levels versus actual of digitoxin are approximately ten times greater than digitoxin concentration of serum digitoxin standards. those of digoxin, and the half-lives of these drugs in The slope and intercept of the line were determined by serum differ by a factor of four. These facts have been the linear least-squares technique. combined into a series of rules which allow the technologist to distinguish between digoxin and digitoxin Discussion in a sample and provide a level of the drug that has been corrected for crossreactivity. Figure 2 shows the chemical structures of four cardiac glycosides: digoxin, digitoxin, cedilanid, and In 1972 Edmonds et al. ( 1) published data on the crossreactivity of digitoxin in the digoxin radioim­ TABLE 1. Crossreactivity of Digitoxin in Digoxin RIA munoassay (Tables 1 and 2). They showed the slopes Measured level of of digoxin-digitoxin cross reactivity plots to be linear. Digitoxin added (ng/mll digoxin (ng/mll Kuno-Sakai et al.
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]