DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2009/0246185 A1 Kishida Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read 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. US 2009/0246.185 A1 Oct. 1, 2009 CARDAC DYSFUNCTION-AMELORATING orporeal energy source. In human, coenzyme Q10 in which AGENT OR CARDAC the side chain of coenzyme Q has 10 repeat structures is the FUNCTION-MANTAININGAGENT main component, and aids the life activity of cells and tissues. In Japan, oxidized coenzyme Q10 is used as a drug for con TECHNICAL FIELD gestive heart failure, and in Europe and the United States, 0001. The present invention relates to a cardiac dysfunc oxidized coenzyme Q10 is widely used as a health food. tion-ameliorating agent or cardiac function-maintaining There are reports on the effectiveness for cardiac diseases agent comprising reduced coenzyme Q as an active ingredi other than cardiac failure. Such as angina pectoris (non-patent ent. reference 1), myocardial infarction (non-patent reference 2) and the like, as well as hypertension (non-patent reference 3). BACKGROUND ART 0006 An important characteristic of coenzyme Q10 is its high Safety. It has been reported that consecutive administra 0002 Cardiac disease is one of the important causes of death for Japanese people, of which angina pectoris, myocar tion of 1200 mg/kg/day for 52 weeks in a chronic toxicity test dial infarction and cardiac failure are highly important as the of oxidized coenzyme Q10 in rats did not show a toxic influ pathology potentially directly causing death. "Easily-fa ence (non-patent reference 4). For human (body weight 50 tigued, “short breath”, “episode of chest pain”, “palpita kg), 1200 mg/kg/day corresponds to 60 g/day. In view of the tion”, “dizziness, faint” and the like are symptoms frequently fact that the usual dosage of oxidized coenzyme Q10 used as associated with cardiac diseases. For example, "episode of a health food in Europe and the United States is 100-300 chest pain' is a symptom mostly related to angina pectoris mg/day, coenzyme Q10 is an extremely highly safe Supple myocardial infarction, and “easily-fatigued, “short breath’ ment material. and "palpitation' are symptoms mostly related to cardiac 0007. It is known that generally about 40-90% of coen failure. Angina pectoris is a state in which arteriosclerosis is Zyme Q in the living organisms is in a reduced form. It has formed in the coronary of the heart, the arteriosclerosis causes also been reported that a pharmaceutical composition con stenosis which prevents sufficient supply of blood to the taining reduced coenzyme Q is Superior in oral absorbability cardiac muscle, and the cardiac muscle runs short of oxygen (patent reference 3). However, reduced coenzyme Q is diffi and produces a chest pain. Myocardial infarction refers to the cult to handle since it is easily oxidized by oxygen in the air, pathology where the coronary is completely obstructed and and the oxidized coenzyme Q is generally conventionally blood supply is completely prevented, thus causing a partial commercially available and is used as a pharmaceutical agent death of the heart. Cardiac failure refers to the pathology where the hematological Supply is insufficient for the sys orfood because once ingested, oxidized coenzyme Q is con temic demand, since the pumping function of the heart verted to reduced coenzyme Q in the body. As mentioned became lower. Cardiac failure is the pathology that com above, the action of oxidized coenzyme Q on the cardiac monly occurs at late stages of any cardiac diseases, which function has already been confirmed and oxidized coenzyme shows characteristic symptoms of short breath, generalized Q has been put to practical use. Due to the aforementioned fatigability, palpitation, Swelling of lower leg and the like. circumstances, however, application of reduced coenzyme Q 0003 Angina pectoris, myocardial infarction and cardiac itself to a cardiac function associated disease has not been failure are treated by a drug therapy, a catheter treatment, a tried. For example, there are reports on the methods for the Surgical treatment and the like. Particularly, in cardiac dis treatment and/or prophylaxis of blood vessel diseases char eases, a drug therapy is highly important among the treat acterized by a shortage of nitric oxide (NO), comprising ments. Therefore, many drugs are currently used for the treat combining a therapeutic agent for angina pectoris and an ment of cardiac diseases. Nevertheless, cardiac disease is the antioxidant, which include a case reciting oxidized coenzyme second major cause of death next to cancer for Japanese Q and reduced coenzyme Q as simple examples of the anti people, and the number thereof keeps rising due to the west oxidant (patent reference 4), and a report on a composition ernized eating habits and lifestyle. In the circumstances, there that enhances cell energy metabolism by combining oxidized is a demand for the development of a pharmaceutical product coenzyme Q10 or reduced coenzyme Q10 with two or more or functional food showing an ameliorating or prophylactic kinds of cytochromes a, b, c and the like (patent reference 5). action on cardiac dysfunction, which is safe and can be con Nevertheless, the action of reduced coenzyme Q itself on the tinuously ingested every day. cardiac function has not been confirmed. 0004 Such reports relating to a composition having a car diac dysfunction-ameliorating or cardiac function-maintain 0008 patent reference 1: JP-A-2005-132758 ing action concern a composition or food and drink contain 0009 patent reference 2: JP-A-2005-239581 ing, as an active ingredient, arachidonic acid or a compound (0010 patent reference 3: JP-A-10-109933 containing arachidonic acid as a constituent fatty acid (patent 00.11 patent reference 4: National Publication of Interna reference 1), a composition containing pycnogenol (patent tional Patent Application No. 2003-5 14020 reference 2) and the like. 0005 Coenzyme Q is an essential component widely dis 0012 patent reference 5: National Publication of Interna tributed in living organisms from bacterium to mammal, and tional Patent Application No. 2004-518712 is known to be an electron transport system constituent com (0013 non-patent reference 1: Am J Cardiol 1985; 56(4): ponent of mitochondria in the cells of a living body. Coen 247-51. Zyme Q functions as a transport component in the electron (0014) non-patent reference 2: Mol Cell Biochem 2003: transport system by repeating oxidization and reduction in 246(1-2): 75-82. mitochondria, and is one of the coenzymes necessary for 0015 non-patent reference 3: Biofactors 2003; 18(1-4): producing ATP (adenosine triphosphate), which is an intrac 91-100. US 2009/0246.185 A1 Oct. 1, 2009 0016 non-patent reference 4: J Agric Food Chem 1999; 0029 11 A method of controlling cardiac function, com 47: 3756-3763. prising administering a cardiac dysfunction-ameliorating agent or cardiac function-maintaining agent comprising a DISCLOSURE OF THE INVENTION reduced coenzyme Q represented by the following formula Problems to be Solved by the Invention (1): 0017. An object of the present invention is to provide a highly safe composition Superior in a cardiac dysfunction (1) ameliorating or cardiac function-maintaining action. OH Means of Solving the Problems H3CO CH3 0018. The present inventors have conducted intensive studies in an attempt to solve the aforementioned problems and found that use of particularly, reduced coenzyme Q10 from among highly safe coenzyme Q is effective for the OH amelioration of cardiac dysfunction and maintenance of car diac function. Accordingly, the present invention is as fol wherein n is an integer of 1-12, as an active ingredient, to a lows. Subject of administration. 0019 1A cardiac dysfunction-ameliorating agent or car 0030 12. The method of 11, wherein the aforemen diac function-maintaining agent comprising reduced coen tioned Subject of administration is a healthy human or healthy Zyme Q represented by the following formula (1): animal having a potential risk of cardiac dysfunction. 0031. 13. The method of 11, wherein the aforemen (1) tioned subject of administration is suffering from cardiac OH dysfunction and under a treatment thereof, and the method further comprises administering the aforementioned cardiac H3CO CH3 dysfunction-ameliorating agent or cardiac function-main taining agent as an aid of the treatment.
Load more

Recommended publications
  • Upregulation of Peroxisome Proliferator-Activated Receptor-Α And
    Upregulation of peroxisome proliferator-activated receptor-α and the lipid metabolism pathway promotes carcinogenesis of ampullary cancer Chih-Yang Wang, Ying-Jui Chao, Yi-Ling Chen, Tzu-Wen Wang, Nam Nhut Phan, Hui-Ping Hsu, Yan-Shen Shan, Ming-Derg Lai 1 Supplementary Table 1. Demographics and clinical outcomes of five patients with ampullary cancer Time of Tumor Time to Age Differentia survival/ Sex Staging size Morphology Recurrence recurrence Condition (years) tion expired (cm) (months) (months) T2N0, 51 F 211 Polypoid Unknown No -- Survived 193 stage Ib T2N0, 2.41.5 58 F Mixed Good Yes 14 Expired 17 stage Ib 0.6 T3N0, 4.53.5 68 M Polypoid Good No -- Survived 162 stage IIA 1.2 T3N0, 66 M 110.8 Ulcerative Good Yes 64 Expired 227 stage IIA T3N0, 60 M 21.81 Mixed Moderate Yes 5.6 Expired 16.7 stage IIA 2 Supplementary Table 2. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of an ampullary cancer microarray using the Database for Annotation, Visualization and Integrated Discovery (DAVID). This table contains only pathways with p values that ranged 0.0001~0.05. KEGG Pathway p value Genes Pentose and 1.50E-04 UGT1A6, CRYL1, UGT1A8, AKR1B1, UGT2B11, UGT2A3, glucuronate UGT2B10, UGT2B7, XYLB interconversions Drug metabolism 1.63E-04 CYP3A4, XDH, UGT1A6, CYP3A5, CES2, CYP3A7, UGT1A8, NAT2, UGT2B11, DPYD, UGT2A3, UGT2B10, UGT2B7 Maturity-onset 2.43E-04 HNF1A, HNF4A, SLC2A2, PKLR, NEUROD1, HNF4G, diabetes of the PDX1, NR5A2, NKX2-2 young Starch and sucrose 6.03E-04 GBA3, UGT1A6, G6PC, UGT1A8, ENPP3, MGAM, SI, metabolism
    [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]
  • 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]
  • NINDS Custom Collection II
    ACACETIN ACEBUTOLOL HYDROCHLORIDE ACECLIDINE HYDROCHLORIDE ACEMETACIN ACETAMINOPHEN ACETAMINOSALOL ACETANILIDE ACETARSOL ACETAZOLAMIDE ACETOHYDROXAMIC ACID ACETRIAZOIC ACID ACETYL TYROSINE ETHYL ESTER ACETYLCARNITINE ACETYLCHOLINE ACETYLCYSTEINE ACETYLGLUCOSAMINE ACETYLGLUTAMIC ACID ACETYL-L-LEUCINE ACETYLPHENYLALANINE ACETYLSEROTONIN ACETYLTRYPTOPHAN ACEXAMIC ACID ACIVICIN ACLACINOMYCIN A1 ACONITINE ACRIFLAVINIUM HYDROCHLORIDE ACRISORCIN ACTINONIN ACYCLOVIR ADENOSINE PHOSPHATE ADENOSINE ADRENALINE BITARTRATE AESCULIN AJMALINE AKLAVINE HYDROCHLORIDE ALANYL-dl-LEUCINE ALANYL-dl-PHENYLALANINE ALAPROCLATE ALBENDAZOLE ALBUTEROL ALEXIDINE HYDROCHLORIDE ALLANTOIN ALLOPURINOL ALMOTRIPTAN ALOIN ALPRENOLOL ALTRETAMINE ALVERINE CITRATE AMANTADINE HYDROCHLORIDE AMBROXOL HYDROCHLORIDE AMCINONIDE AMIKACIN SULFATE AMILORIDE HYDROCHLORIDE 3-AMINOBENZAMIDE gamma-AMINOBUTYRIC ACID AMINOCAPROIC ACID N- (2-AMINOETHYL)-4-CHLOROBENZAMIDE (RO-16-6491) AMINOGLUTETHIMIDE AMINOHIPPURIC ACID AMINOHYDROXYBUTYRIC ACID AMINOLEVULINIC ACID HYDROCHLORIDE AMINOPHENAZONE 3-AMINOPROPANESULPHONIC ACID AMINOPYRIDINE 9-AMINO-1,2,3,4-TETRAHYDROACRIDINE HYDROCHLORIDE AMINOTHIAZOLE AMIODARONE HYDROCHLORIDE AMIPRILOSE AMITRIPTYLINE HYDROCHLORIDE AMLODIPINE BESYLATE AMODIAQUINE DIHYDROCHLORIDE AMOXEPINE AMOXICILLIN AMPICILLIN SODIUM AMPROLIUM AMRINONE AMYGDALIN ANABASAMINE HYDROCHLORIDE ANABASINE HYDROCHLORIDE ANCITABINE HYDROCHLORIDE ANDROSTERONE SODIUM SULFATE ANIRACETAM ANISINDIONE ANISODAMINE ANISOMYCIN ANTAZOLINE PHOSPHATE ANTHRALIN ANTIMYCIN A (A1 shown) ANTIPYRINE APHYLLIC
    [Show full text]
  • Phosphodiesterase (PDE)
    Phosphodiesterase (PDE) Phosphodiesterase (PDE) is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many other families of phosphodiesterases, including phospholipases C and D, autotaxin, sphingomyelin phosphodiesterase, DNases, RNases, and restriction endonucleases, as well as numerous less-well-characterized small-molecule phosphodiesterases. The cyclic nucleotide phosphodiesterases comprise a group of enzymes that degrade the phosphodiester bond in the second messenger molecules cAMP and cGMP. They regulate the localization, duration, and amplitude of cyclic nucleotide signaling within subcellular domains. PDEs are therefore important regulators ofsignal transduction mediated by these second messenger molecules. www.MedChemExpress.com 1 Phosphodiesterase (PDE) Inhibitors, Activators & Modulators (+)-Medioresinol Di-O-β-D-glucopyranoside (R)-(-)-Rolipram Cat. No.: HY-N8209 ((R)-Rolipram; (-)-Rolipram) Cat. No.: HY-16900A (+)-Medioresinol Di-O-β-D-glucopyranoside is a (R)-(-)-Rolipram is the R-enantiomer of Rolipram. lignan glucoside with strong inhibitory activity Rolipram is a selective inhibitor of of 3', 5'-cyclic monophosphate (cyclic AMP) phosphodiesterases PDE4 with IC50 of 3 nM, 130 nM phosphodiesterase. and 240 nM for PDE4A, PDE4B, and PDE4D, respectively. Purity: >98% Purity: 99.91% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg Size: 10 mM × 1 mL, 10 mg, 50 mg (R)-DNMDP (S)-(+)-Rolipram Cat. No.: HY-122751 ((+)-Rolipram; (S)-Rolipram) Cat. No.: HY-B0392 (R)-DNMDP is a potent and selective cancer cell (S)-(+)-Rolipram ((+)-Rolipram) is a cyclic cytotoxic agent. (R)-DNMDP, the R-form of DNMDP, AMP(cAMP)-specific phosphodiesterase (PDE) binds PDE3A directly.
    [Show full text]
  • Analysis of Gene Expression from Systemic Lupus Erythematosus Synovium
    bioRxiv preprint doi: https://doi.org/10.1101/2020.06.19.123307; this version posted June 21, 2020. 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. Analysis of Gene Expression from Systemic Lupus Erythematosus Synovium Reveals a Profile of Activated Immune Cells and Inflammatory Pathways Erika L. Hubbarda,*, Michelle D. Catalinaa,b, Sarah Heuera,c, Prathyusha Bachalia, Robert Robla, Nicholas S. Geracia,d, Amrie C. Grammera,#, Peter E. Lipskya,# aRILITE Research Institute and AMPEL BioSolutions LLC; 250 West Main Street Suite #300 Charlottesville, VA 22902, USA. *Address correspondence to [email protected]; 250 West Main Street Suite 300, Charlottesville, VA 22902, USA. bPresent address: EMD Serono Research & Development Institute, 45 A Middlesex Turnpike Billerica, MA 01821 cPresent address: The Jackson Laboratory, Tufts Graduate School of Biomedical Sciences, 600 Main Street Bar Harbor, ME 04609, USA dPresent address: Profiler Business Unit, Genedata Inc, 1 Cranberry Hill, Lexington, MA 02421, USA #Contributed equally to this work 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.06.19.123307; this version posted June 21, 2020. 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. ABSTRACT Arthritis is a common manifestation of systemic lupus erythematosus (SLE) yet understanding of the underlying pathogenic mechanisms remains incomplete. We, therefore, interrogated gene expression profiles of SLE synovium to gain insight into the nature of lupus arthritis (LA), using osteoarthritis (OA) and rheumatoid arthritis (RA) as comparators.
    [Show full text]
  • Pharmaceutical Appendix to the Harmonized Tariff Schedule
    Harmonized Tariff Schedule of the United States (2019) Revision 13 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2019) Revision 13 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.
    [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]
  • Xagrid, INN-Anagrelide
    SCIENTIFIC DISCUSSION 1. Introduction Anagrelide hydrochloride monohydrate is a novel imidazoquinazoline originally developed as an inhibitor of platelet aggregation but subsequently found to have value as a platelet-lowering agent for the treatment of patients suffering from Essential thrombocythaemia (ET). ET is one of a number of chronic myeloproliferative disorders characterised by an elevated platelet count due to an autonomous clonal proliferation of bone marrow megakaryocytes. The underlying cause of this proliferation is unknown. Platelet function is generally normal and the cells are able to undergo aggregation and to participate in the haemostatic process in a more or less normal manner. The diagnosis is one of exclusion of reactive causes and other myeloproliferative disorders (MPDs) according to internationally agreed criteria of the Polycythaemia Vera Study Group (PVSG). The main criterion is a sustained platelet level of >600 x 109/L for more than two months. It is estimated that the prevalence of ET in the European Union (EU) is 2-3 per 10,000 persons. ET is a condition that may affect anyone at any stage of life from childhood although the median age of presentation is 60 years. Literature and clinical experience indicate a preponderance of female patients between the ages of 25 and 50 years. Up to two thirds of patients with ET are asymptomatic and a significant number of patients are now being diagnosed as an incidental consequence of the analysis of full blood counts for other health reasons. Generally, the older patient is more likely to be symptomatic at presentation, although younger patients may present with major complications.
    [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]
  • 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]