DOCSLIB.ORG

United States Patent [191 [11] Patent Number: 4,707,360 Brasey [45] Date of Patent: Nov

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
United States Patent [191 [11] Patent Number: 4,707,360 Brasey [45] Date of Patent: Nov United States Patent [191 [11] Patent Number: 4,707,360 Brasey [45] Date of Patent: Nov. 17, 1987 [54] VASCULOPROTECI‘ING [58] Field of Search .............. .. 424/941, DIG. 15, 94; PHARMACEUTICAL COMPOSITIONS 514/25, 27, 456 [75] Inventor: Pierre-Noel Brasey, Geneva, [56] References Cited Switzerland PUBLICATIONS Merck Index, 9th ed. Nos. 1240, and 9496, 1976. [73] Assignee: Seuref A.G., Vaduz, Liechtenstein Primary Examiner—J. R. Brown [21] Appl. No.: 857,152 Assistant Examiner—John W. Rollins, Jr. Attorney, Agent, or Firm-Bucknam and Archer [22] Filed: Apr. 29, 1986 [57] ABSTRACT [30] Foreign Application Priority Data Pharmaceutical compositions having vasculoprotecting Apr. 30,1985 [CH] Switzerland ....................... .. 1826/85 activity, containing an ubiquinone compound together with one or more compounds of flavanoid, heparinoid, [51] Int. Cl.4 ................... .. A61K 37/48; A61K 31/70; terpenic or glycosidic structure, such as escin, troxeru A61K 31/35 tin, asiaticoside, heparin, delphinidin, tribenoside. [52] US. Cl. ................................... .. 424/941; 5l4/25; 514/27; 514/456; 424/DIG. 15 2 Claims, No Drawings 4,707,360 1 2 Now it has surprisingly been found that ubiquinone VASCULOPROTECI'ING PHARMACEUTICAL compounds, particularly Coenzyme Q10, synergistically COMPOSITIONS enhance the activity of known vasculoprotecting agents, particularly chalones, aurones, ?avones, flava The present invention relates to pharmaceutical com 5 nones, flavanols, flavanonols, flavanediols, leukoan positions containing as the active ingredient one ubiqui thocyanidines, cumarins, hesperidins,_ catechins, an none compound together with known compounds suit thocyanidines, natural or semisynthetic derivatives able for vascular therapy. thereof, or vegetal extracts containing them. Examples of said vasculoprotecting compounds are By means of the combination of the present inven those having ?avonoid, terpenic, glycosidic, heparinoid 10 tion, a marked increase in therapeutic action is obtained, structures, such as escin, rutin, troxerutin, diosmin, in comparison with the one of the single components, asiaticoside, hesperidin, tribenoside, etc. - without toxic or side-effects. The components of the compositions according to The pharmaco-toxycologic tests carried out will be the invention display a synergistic action on the regula hereinafter described, in order to illustrate the advan tion of vascular activity and permeability. 15 tages of the compositions of the present invention. Moreover, said compositions prevent trophic and Coenzyme Q10 is known to have a low toxicity, its metabolic tissular changes as well as those from anoxic DLSQ in rats and mice being respectively higher than conditions, due to impaired vascularization. 500 and 250 mg/kg by intraperitoneal administration, Among the vasculoprotecting agents, particularly and higher than 4 g/kg by subcutaneous administration. known are ?avonoids, whose effectiveness as capillary Flavonoids and heparinoids are also known to be protecting agents, antiedemics and cicatrizants in vasal little toxic, and the combination thereof with Coenzyme diseases has been widely described in literature (Bohr Q10 shows no changes in the toxicity values of the com D. F.——J. Pharmacol. Exp. Ther., 97-243-1949; Gugler ponents. 1:1 Combination of Coenzyme Q10 and an R.—Ges. Arch. Exp. Pathol. Pharm.—274-R45-l972; thocyanine, hydroxyethylrutoside or catechin,_showed Haeger K.—Zbl. Phlebol., 6-526-1967; Rozkoch K.— 25 DL50 values higher than 1 g/kg in both rats and mice, Europ. J. Clin. Pharmacol., 3-243-1971; Allen S.—Prac by oral administration. tioner, 205-221-1970). Also the chronic toxicity tests carried out in the rat Similar activities were disclosed for heparin and by oral daily administration of the above combinations heparinoids (Witte S., Thromb. Diath. Hemorrhag, in 1:1 ratio for 30 consecutive days showed no patho 2-146-1958; Jacques L. B.——Ann. NY. Acad. Sci., logic changes in the body weight and in hemathological 115-781-1969; Nicolaides A. N.—Lancet, 2-890-1972). and biochemical parameters. All the ?avonoids, at the vasal level, act to regulate On the contrary, the above combinations proved to the entry of calcium into the cells (Ludwig O.—Med. be surprisingly effective in different pharmacological Welt, 16-1181-1942) and to inhibit any increased effect tests, such as wound-healing time in experimental of lysosomial enzymes, related to pathological condi 35 wounds in the rabbit, rupture resistance of cicatrices in tions (Niches P.-—Angiologica, 8-297-1971). the mouse, antiedemic activitiy in the rat, activity on Moreover, it should be pointed out that the synthesis capillary permeability and ergotamine arteritis in the of glycosaminoglycans, which are among the main rat. components of vasal wall and control its hydropexic In all the above tests a marked synergism between action as well as ion passage, takes place mainly by 40 Coenzyme Q10 and the other vasoprotecting com activation of Golgi apparatus, whose function is condi pounds was evidenced, the obtained results being sur tioned by the availability of respiratory chain, related to prisingly more favourable than the ones obtained using Coenzyme Q10 (Balasz E.—Arthritis-Arthrose Verlag the single components. Haan Huber, Bern Wien, 46-1971; Crane F. L.——“Bi The tests were carried out combining Coenzyme Q10 omedical and Clinical Aspects of Coenzyme Q”, Folk with O-(B-hydroxyethylrutoside), escin (a saponin from ers K. Ed., Vol. 1, Elsevier Amsterdam, 1977, p, 3; Esculus hippocastanum), tribenoside (ethyl 3,5,6-tri-O Lenaz G.—Drugs Exptl. Clin. Res., 10-481-1984). benzyl-S-glycofuronoside), delphinidin (anthocyani A de?ciency in oxygen diffusion and utilization, as din), and total extract of Centella asiatica (asiaticoside). well as tissular hypoxic conditions, have been also indi The tests on wound healing activity of the composi cated as causes of vascular diseases and atherosclerosis 50 tions of the invention were carried out on cutaneous (Robertson A. L.——Progr. Biochem. Pharmacol., Vol. wounds in the rat orally treated with prednisolone, 4, p. 305, Karger, Basel, 1968; Zempleny T.—Symposia according to the procedure of J. J. Morton (Morton J. Angiologica Santoriana—-4 Int. Symp., Fribourg-Nyon J. P., Malone M. H.—Arch. Int. Pharmacodyn., l972--Angiologica, 9-429-1972). 196-117-1972). Coenzyme Q10 is known to control the transport of 55 The cicatrization of the cutis of the back of the rat mytochondrial electrons, and consequently to play a previously scari?ed was delayed by oral treatment with role in oxygen utilization and tissue metabolism, since 0.25 mg/kg of prednisolone. tissular and cellular energetic processes are related to The test composition was applied on the wound, after hydrogenion transport (Morton R. A.—Nature, appropriate suspension at different concentrations. 182-1764-1958; Gale P. H.—Arch. Biochem. Biophys., 60 The area of the wound on the third day of treatment 93-211-1961). was measured: the results reported in the following In fact, Coenzyme Q10 avoids the damages caused by Table I evidence a marked synergistic action of the cellular lypoperoxydation, intracellular calcium in compositions of the invention. crease and lysosomial enzyme release, which markedly affect normal cellular and tissular vasal functioning 65 TABLE 1 (Lehedev A. V.—J. Mol. Cell. Cardiol, 14 (Suppl. 3) Dose % 99-1982; Littarru G. P.—Drugs Exptl. Clin. Res., Compound mg/cm2 cutis Reduction 10491-1984). A 100 22 4,707,360 3 4 of pharmaceutical technique, using pharmaceutically TABLE l-continued acceptable carriers or diluents. Dose % Non-limiting examples of suitable compositions of the Compound mg/cm2 cutis Reduction invention are reported hereinbelow. B l0 l5 5 C 50 11 TABLETS D 25 18 E 25 ll Coenzyme Q10 10 mg+escin 20 mg A + B 100 + 10 65 Coenzyme Q10 50 mg+escin 20 mg A + C 100 + 50 40 Coenzyme Q10 10 mg+hydroxyethylrutoside 300 mg A + D 100 + Z5 56 10 Coenzyme Q10 50 mg+hydroxyethylrutoside 500 mg A + E 100 + 25 63 Coenzyme Q10 10 mg+asiaticoside 10 mg A = Coenzyme Q10 Coenzyme Q10 50 mg+asiaticoside 10 mg B = Delphinidin C = Escin Coenzyme Q10 l0 mg+tribenoside 400 mg D = Tribenoside Coenzyme Q10 50 mg+tribenoside 500 mg E = Asiaticoside. 15 Coenzyme Q10 10 mg+delphinidin 100 mg Coenzyme Q10 50 mg+delphinidin 200 mg. Oral administration of the compositions of the inven tion also surprisingly increased the rupture resistance of SUGAR-COATED PILLS scars induced in the mouse by incision of cutis of the Coenzyme Q10 10 mg+escin 20 mg back. The treatment was continued during 3 consecu . 20 Coenzyme Q10 50 mg+hydroxyethylrutoside 500 mg . tlve days after surgical suturation of the wound, after Coenzyme Q10 10 mg+tribenoside 500 mg this period the cutis portion containing the scar was Coenzyme Q10 50 mg+tribenoside 500 mg removed, one end thereof was ?xed to a support and the other one was subjected to continuous traction (110 CAPSULES g/minute). The rupture strength results are reported in 25 Coenzyme Q10 10 mg+escin 20 mg Table 2 hereinbelow. Coenzyme Q10 10 mg+tribenoside 400 mg TABLE 2 Coenzyme Q10 50 mg+tribenoside 500 mg Dose % Rupture CREAMS mg/kg resistance Compound (per 05) (in grams) 30 Coenzyme Q10 1% +escin 1% A 25 19 Coenzyme Q10 l%+hydroxyethylrutoside 2% B 100 21 Coenzyme Q10 l%+asiaticoside 1% C 25 16 Coenzyme Q10 l%+tribenoside 1% D 50 15 Coenzyme Q10 l%+delphinidin 1%. E 25 13 A + B 25 + 100 75 35 OINTMENTS A + C 25 + 25 82 A + D 25 + 50 so Coenzyme Q10 l%+escin 1% A + E 25 + 25 95 Coenzyme Q10 1% +sodium heparin 10,000 IU/100 g of A, B, C, D, E = vide Table l. ointment 40 Coenzyme Q10 l%+natural heparinoid 70,000 IU/ g The capillary resistance tests were carried out ac Coenzyme Q10 1% +sulfate glucuronylglycosamino cording to the procedure of Charlier R. (Charlier R., glicane(heparinoid) 200 mg, equal to 400 UHC. Hosslet A., Color M.——Arch. Int. Physiol. Biochem, 71-1-1963), by oral treatment for 3 consecutive days of SUPPOSITORIES rats, previously feeded for 2 weeks with a diet lacking in 45 Coenzyme Q10 50 mg+escin 50 mg vitamin P.
Load more

Recommended publications
  • Evidências Sobre Tratamentos Clínicos Conservadores Para Doença
    www.rbmfc.org.br ARTIGOS DE REVISÃO Evidências sobre tratamentos clínicos conservadores para doença hemorroidária Evidence on conservative clinical treatments for haemorrhoids Evidencias sobre tratamientos clínicos conservadores para la enfermedad hemorroidal Fernanda da Silva Barbosa. Universidade Federal de Santa Catarina (UFSC). Florianópolis, SC, Brasil. [email protected] (Autora correspondente) Jardel Corrêa de Oliveira. Secretaria Municipal de Saúde (SMS). Florianópolis, SC, Brasil. [email protected] Charles Dalcanale Tesser. Universidade Federal de Santa Catarina (UFSC). Florianópolis, SC, Brasil. [email protected] Resumo Objetivo: o objetivo desta avaliação de tecnologia em saúde foi analisar as evidências sobre tratamentos clínicos conservadores para doença Palavras-chave: Avaliação da Tecnologia hemorroidária utilizáveis na Atenção Primária à Saúde. Métodos: buscou-se no Embase, LILACS e MEDLINE via Pubmed por meta-análises, revisões Biomédica sistemáticas e ensaios clínicos controlados e aleatorizados, publicados até dezembro de 2012, sem limite de linguagem. Os estudos deveriam avaliar Terapêutica os efeitos dos tratamentos clínicos conservadores (fibras ou laxantes, flavonoides, analgésicos, corticosteroides, banhos de assento ou pomadas de Hemorroidas nitroglicerina) comparados a placebo ou entre si. Os desfechos considerados foram: melhora global dos sintomas, sangramento, prurido, dor, prolapso Atenção Primária à Saúde e efeitos adversos. Resultados: uma meta-análise demonstrou que fibras promovem melhora global dos sintomas e do sangramento e diminuem a recorrência após procedimentos ambulatoriais. Três meta-análises mostraram a eficácia de flavonoides para sangramento agudo e pós-operatório, melhora global dos sintomas, exsudação perianal e recorrência após episódio agudo. Não houve diferença estatística para prurido, dor, prolapso ou efeitos adversos nos dois casos. Flavonoides do tipo rutosídeos reduziram sintomas em gestantes, apesar da insuficiência dos dados para comprovar sua segurança.
    [Show full text]
  • Index to the NLM Classification 2011
    National Library of Medicine Classification 2011 Index Disease see Tyrosinemias 1-8 5,12-diHETE see Leukotriene B4 1,2-Benzopyrones see Coumarins 5,12-HETE see Leukotriene B4 1,2-Dibromoethane see Ethylene Dibromide 5-HT see Serotonin 1,8-Dihydroxy-9-anthrone see Anthralin 5-HT Antagonists see Serotonin Antagonists 1-Oxacephalosporin see Moxalactam 5-Hydroxytryptamine see Serotonin 1-Propanol 5-Hydroxytryptamine Antagonists see Serotonin Organic chemistry QD 305.A4 Antagonists Pharmacology QV 82 6-Mercaptopurine QV 269 1-Sar-8-Ala Angiotensin II see Saralasin 7S RNA see RNA, Small Nuclear 1-Sarcosine-8-Alanine Angiotensin II see Saralasin 8-Hydroxyquinoline see Oxyquinoline 13-cis-Retinoic Acid see Isotretinoin 8-Methoxypsoralen see Methoxsalen 15th Century History see History, 15th Century 8-Quinolinol see Oxyquinoline 16th Century History see History, 16th Century 17 beta-Estradiol see Estradiol 17-Ketosteroids WK 755 A 17-Oxosteroids see 17-Ketosteroids A Fibers see Nerve Fibers, Myelinated 17th Century History see History, 17th Century Aardvarks see Xenarthra 18th Century History see History, 18th Century Abate see Temefos 19th Century History see History, 19th Century Abattoirs WA 707 2',3'-Cyclic-Nucleotide Phosphodiesterases QU 136 Abbreviations 2,4-D see 2,4-Dichlorophenoxyacetic Acid Chemistry QD 7 2,4-Dichlorophenoxyacetic Acid General P 365-365.5 Organic chemistry QD 341.A2 Library symbols (U.S.) Z 881 2',5'-Oligoadenylate Polymerase see Medical W 13 2',5'-Oligoadenylate Synthetase By specialties (Form number 13 in any NLM
    [Show full text]
  • Medical Management of Lower Extremity Chronic Venous Disease
    Medical management of lower extremity chronic venous disease Authors: Patrick C Alguire, MD, FACP Barbara M Mathes, MD, FACP, FAAD Section Editors: John F Eidt, MD Joseph L Mills, Sr, MD Deputy Editor: Kathryn A Collins, MD, PhD, FACS Contributor Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jul 2020. | This topic last updated: Apr 22, 2020. INTRODUCTION Venous hypertension is associated with histologic and ultrastructural changes in the capillary and lymphatic microcirculation that produce important physiologic changes, which include capillary leak, fibrin deposition, erythrocyte and leukocyte sequestration, thrombocytosis, and inflammation. These processes impair oxygenation of the skin and subcutaneous tissues. The clinical manifestations of severe venous hypertension and tissue hypoxia are edema, hyperpigmentation, subcutaneous fibrosis, and ulcer formation. The medical management of chronic venous disease with and without ulceration is discussed here. The etiology, presentation, and pathophysiology of chronic venous disorders are discussed elsewhere: ●(See "Classification of lower extremity chronic venous disorders".) ●(See "Clinical manifestations of lower extremity chronic venous disease".) ●(See "Pathophysiology of chronic venous disease".) ●(See "Diagnostic evaluation of lower extremity chronic venous insufficiency".) OVERVIEW Treatment goals for patients with chronic venous disease include improvement of symptoms, reduction of edema, prevention and treatment of lipodermatosclerosis (picture 1), and healing of ulcers [1,2]. An algorithm for the medical management of venous insufficiency is based upon available data and published recommendations (algorithm 1) [3-5]. Lipodermatosclerosis Picture 1 Skin induration, redness, and hyperpigmentation involving the lower third of the leg in a patient with stasis dermatitis and lipodermatosclerosis.
    [Show full text]
  • Micronised Purified Flavonoid Fraction a Review of Its Use in Chronic Venous Insufficiency, Venous Ulcers and Haemorrhoids
    Drugs 2003; 63 (1): 71-100 ADIS DRUG EVALUATION 0012-6667/03/0001-0071/$33.00/0 © Adis International Limited. All rights reserved. Micronised Purified Flavonoid Fraction A Review of its Use in Chronic Venous Insufficiency, Venous Ulcers and Haemorrhoids Katherine A. Lyseng-Williamson and Caroline M. Perry Adis International Limited, Auckland, New Zealand Various sections of the manuscript reviewed by: C. Allegra, Servizio di Angiologia, Ospedale San Giovanni, Rome, Italy; J. Bergan, Vein Institute of La Jolla, La Jolla, California, USA; E. Bouskela, Laboratório de Pesquisas em Microcirculação, Universidade do Estado do Rio De Janeiro, Rio De Janeiro, Brazil; D.L. Clement, Department of Cardiology, University Hospital, Ghent, Belgium; P.D. Coleridge Smith, Department of Surgery, University College London Medical School, The Middlesex Hospital, London, England; P. Godeberge, Unité de Proctologie Médico-Chirurgicale, Institut Mutaliste Montsouris, Paris, France; Y.-H. Ho, School of Medicine, James Cook University, Townsville, Queensland, Australia; A. Jawien, Department of Surgery, Ludwik Rydygier University Medical School, Bydgoszcz, Poland; M.C. Misra, General Surgery Department, Mafraq Hospital, Abu Dhabi, United Arab Emirates; A.-A. Ramelet, Place Benjamin-Constant, Lausanne, Switzerland; G.W. Schmid-Schönbein, Institute of Biomedical Engineering, University of California, San Diego, California, USA; F. Zuccarelli, Département Angiologie et Phlébologie, Hôpital Saint Michel, Paris, France. Data Selection Sources: Medical literature published in any language since 1980 on micronised purified flavonoid fraction, identified using Medline and EMBASE, supplemented by AdisBase (a proprietary database of Adis International). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.
    [Show full text]
  • Special Issue
    12_DN_1015_BA_COUV_09_DN_020_BA_COUV 20/10/11 09:57 PageC1 ISSN 1286-0107 Special issue Vol 20 • No.1 • 2012 • p1-56 I. UIP CONSENSUS, UIP FELLOWSHIPS . PAGE 5 II. EPIDEMIOLOGY . PAGE 13 III. PATHOPHYSIOLOGY . PAGE 19 IV. INVESTIGATIONS . PAGE 25 V. TREATMENT . PAGE 27 12_DN_1015_BA_COUV_09_DN_020_BA_COUV 20/10/11 09:57 PageC2 AIMS AND SCOPE Phlebolymphology is an international scientific journal entirely devoted to venous and lymphatic diseases. Phlebolymphology The aim of Phlebolymphology is to pro- vide doctors with updated information on phlebology and lymphology written by EDITOR IN CHIEF well-known international specialists. H. Partsch, MD Phlebolymphology is scientifically sup- Professor of Dermatology, Emeritus Head of the Dermatological Department ported by a prestigious editorial board. of the Wilhelminen Hospital Phlebolymphology has been pub lished Baumeistergasse 85, A 1160 Vienna, Austria four times per year since 1994, and, thanks to its high scientific level, is included in several databases. Phlebolymphology comprises an edito- EDITORIAL BOARD rial, articles on phlebology and lympho- logy, reviews, news, and a congress C. Allegra, MD calendar. Head, Dept of Angiology Hospital S. Giovanni, Via S. Giovanni Laterano, 155, 00184, Rome, Italy P. Coleridge Smith, DM, FRCS CORRESPONDENCE Consultant Surgeon & Reader in Surgery Thames Valley Nuffield Hospital, Wexham Park Hall, Wexham Street, Wexham, Bucks, SL3 6NB, UK Editor in Chief Hugo PARTSCH, MD Baumeistergasse 85 A. Jawien, MD, PhD 1160 Vienna, Austria Department of Surgery Tel: +43 431 485 5853 Fax: +43 431 480 0304 Ludwik Rydygier University Medical School, E-mail: [email protected] Ujejskiego 75, 85-168 Bydgoszcz, Poland Editorial Manager A. N. Nicolaides, MS, FRCS, FRCSE Françoise PITSCH, PharmD Servier International Emeritus Professor at Imperial College 35, rue de Verdun Visiting Professor of the University of Cyprus 92284 Suresnes Cedex, France 16 Demosthenous Severis Avenue, Nicosia 1080, Cyprus Tel: +33 (1) 55 72 68 96 Fax: +33 (1) 55 72 36 18 G.
    [Show full text]
  • VOLUME 32 . OCTOBER 2013 . Suppl. 1 to Issue No. 5
    VOLUME 32 . OCTOBER 2013 . Suppl. 1 to issue No. 5 InternationalInternational AngiologyAngiology the premier association for vein care professionals. The American College of Phlebology (ACP) is comprised of more than 2,000 physicians and allied health care professionals, who are setting the pace and direction for growth in the field of vein care. The ACP offers members advocacy, continuing education and training in the latest science and techniques with the goal of improving standards and the quality of patient care. If you treat or have an interest in venous and lymphatic disease, the ACP is an unequivocal resource for your practice. together we thrive continuing education latest news & information practice management resources improved patient outcomes advancing vein care join today Get more information on how to join by visiting www.phlebology.org or by calling 510.346.6800 advancing vein care www.phlebology.org 510.346.6800 INTERNATIONAL ANGIOLOGY Official Journal of International Union of Angiology, Union Internationale de Phlébologie, Central European Vascular Forum FOUNDER AND EDITOR-IN-CHIEF EMERITUS EDITOR-IN-CHIEF P. BALAS, Athens, Greece A. NICOLAIDES, Nicosia, Cyprus CO-EDITORS A. SCUDERI, Sao Paolo, Brazil (UIP) G. GEROULAKOS, London, UK (Ang. Forum, RSM) J. FAREED, Chicago, USA (IUA) V. STVRTINOVA, Bratislava, Slovakia (CEVF) SPECIALIST COMMITTEE S. A.N. ALAM, Dhaka, Bangladesh J. FLETCHER, Sydney, Australia L. MENDES PEDRO, Lisbon, Portugal F. A. ALLAERT, Dijon, France S. GEORGOPOULOS, Athens, Greece F. MIRANDA Jr, Sao Paolo, Brazil B. AMANN-VESTI, Zurich, Switzerland B. GORENEK, Eskisehir, Turkey J. L. NASCIMENTO Silva, Rio, Brazil P. L. ANTIGNANI, Rome, Italy A. GIANNOUKAS, Larissa, Greece L.
    [Show full text]
  • Dr. Duke's Phytochemical and Ethnobotanical Databases List of Chemicals for Varicose Veins
    Dr. Duke's Phytochemical and Ethnobotanical Databases List of Chemicals for Varicose Veins Chemical Activity Count (+)-ALLOMATRINE 1 (+)-ALPHA-VINIFERIN 1 (+)-CATECHIN 7 (+)-EUDESMA-4(14),7(11)-DIENE-3-ONE 1 (+)-GALLOCATECHIN 2 (+)-HERNANDEZINE 1 (+)-ISOCORYDINE 1 (+)-PRAERUPTORUM-A 1 (+)-PSEUDOEPHEDRINE 1 (+)-SYRINGARESINOL 1 (-)-16,17-DIHYDROXY-16BETA-KAURAN-19-OIC 1 (-)-ACETOXYCOLLININ 1 (-)-ALPHA-BISABOLOL 2 (-)-ARGEMONINE 1 (-)-BETONICINE 1 (-)-BISPARTHENOLIDINE 1 (-)-BORNYL-CAFFEATE 2 (-)-BORNYL-FERULATE 2 (-)-BORNYL-P-COUMARATE 2 (-)-DICENTRINE 1 (-)-EPIAFZELECHIN 1 (-)-EPICATECHIN 3 (-)-EPICATECHIN-3-O-GALLATE 1 (-)-EPIGALLOCATECHIN 1 (-)-EPIGALLOCATECHIN-3-O-GALLATE 2 (-)-EPIGALLOCATECHIN-GALLATE 3 (-)-HYDROXYJASMONIC-ACID 1 Chemical Activity Count (-)-N-(1'-DEOXY-1'-D-FRUCTOPYRANOSYL)-S-ALLYL-L-CYSTEINE-SULFOXIDE 1 (1'S)-1'-ACETOXYCHAVICOL-ACETATE 2 (15:1)-CARDANOL 1 (2R)-(12Z,15Z)-2-HYDROXY-4-OXOHENEICOSA-12,15-DIEN-1-YL-ACETATE 1 (7R,10R)-CAROTA-1,4-DIENALDEHYDE 1 (E)-4-(3',4'-DIMETHOXYPHENYL)-BUT-3-EN-OL 2 1,2,6-TRI-O-GALLOYL-BETA-D-GLUCOSE 1 1,7-BIS(3,4-DIHYDROXYPHENYL)HEPTA-4E,6E-DIEN-3-ONE 1 1,7-BIS(4-HYDROXY-3-METHOXYPHENYL)-1,6-HEPTADIEN-3,5-DIONE 1 1,7-BIS-(4-HYDROXYPHENYL)-1,4,6-HEPTATRIEN-3-ONE 1 1,8-CINEOLE 3 1-(METHYLSULFINYL)-PROPYL-METHYL-DISULFIDE 1 1-O-(2,3,4-TRIHYDROXY-3-METHYL)-BUTYL-6-O-FERULOYL-BETA-D-GLUCOPYRANOSIDE 1 10-ACETOXY-8-HYDROXY-9-ISOBUTYLOXY-6-METHOXYTHYMOL 2 10-DEHYDROGINGERDIONE 1 10-GINGERDIONE 1 11-HYDROXY-DELTA-8-THC 1 11-HYDROXY-DELTA-9-THC 1 12,118-BINARINGIN 1 12-ACETYLDEHYDROLUCICULINE
    [Show full text]
  • Mechanisms of Lower Extremity Vein Dysfunction in Chronic Venous Disease and Implications in Management of Varicose Veins
    Raffetto et al. Vessel Plus 2021;5:36 Vessel Plus DOI: 10.20517/2574-1209.2021.16 Review Open Access Mechanisms of lower extremity vein dysfunction in chronic venous disease and implications in management of varicose veins Joseph D. Raffetto, Raouf A. Khalil Vascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA 02115, USA. Correspondence to: Dr. Raouf A. Khalil, Vascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women’s Hospital, and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. E-mail: [email protected] How to cite this article: Raffetto JD, Khalil RA. Mechanisms of lower extremity vein dysfunction in chronic venous disease and implications in management of varicose veins. Vessel Plus 2021;5:36. https://dx.doi.org/10.20517/2574-1209.2021.16 Received: 8 Feb 2021 Accepted: 10 May 2021 First online: 29 May 2021 Academic Editors: Rene Gordon Holzheimer, Markus Stücker Copy Editor: Xi-Jun Chen Production Editor: Xi-Jun Chen Abstract Chronic venous disease (CVD) is a common venous disorder of the lower extremities. CVD can be manifested as varicose veins (VVs), with dilated and tortuous veins, dysfunctional valves and venous reflux. If not adequately treated, VVs could progress to chronic venous insufficiency (CVI) and lead to venous leg ulcer (VLU). Predisposing familial and genetic factors have been implicated in CVD. Additional environmental, behavioral and dietary factors including sedentary lifestyle and obesity may also contribute to CVD. Alterations in the mRNA expression, protein levels and proteolytic activity of matrix metalloproteinases (MMPs) have been detected in VVs and VLU.
    [Show full text]
  • Reverse Phase Hplc Method Development and Validation for the Simultaneous Quantitative Estimation of Troxerutin and Calcium Dobesilate in Tablets
    International Journal of Pharmacy and Pharmaceutical Sciences Academic Sciences ISSN- 0975-1491 Vol 6, Issue 1, 2014 Research Article REVERSE PHASE HPLC METHOD DEVELOPMENT AND VALIDATION FOR THE SIMULTANEOUS QUANTITATIVE ESTIMATION OF TROXERUTIN AND CALCIUM DOBESILATE IN TABLETS N.J.R. HEPSEBAH, D. NIHITHA, A.ASHOK KUMAR* Department of Pharmaceutical analysis and Quality Assurance, Vijaya college of pharmacy, Munaganur (village), Hayathnagar (mandal), Hyderabad 501511, India. Email:[email protected] Received: 04 Oct 2013, Revised and Accepted: 30 Oct 2013 ABSTRACT Objective: To develop a simple, precise, accurate, linear and rapid Reverse Phase High Performance Liquid Chromatographic (RP-HPLC) method for the simultaneous quantitative estimation of Troxerutin 500 mg and Calcium dobesilate 500 mg in tablets as per ICH guidelines. Methods: The method uses reverse phase column, Enable C18G (250X4.6 mm; 5μ) column and an isocratic elution. Method optimized conditions include a mobile phase of acetonitrile:methanol:0.02M potassium dihydrogen orthophosphate buffer adjusted to pH 4 in the proportion of 25:10:65 v/v, flow rate of 0.5 ml/min and detection wavelength of 210 nm using a UV detector. Results: The developed method resulted in calcium dobesilate eluting at 3.56 min and troxerutin at 6.69 min. The linearity of the method was excellent over the range 62.5-250 μg/ml for both the drugs. The precision is exemplified by relative standard deviations of 0.258% for calcium dobesilate and 0.215% for troxerutin. Accuracy studies revealed % mean recoveries during spiking experiments between 98 and 102. The limit of detection was obtained as 3 ng/mL for Calcium dobesilate and 0.5 µg/mL for Troxerutin, while the limit of quantitation was obtained as 10 ng/mL for Calcium dobesilate and 1µg/mL for Troxerutin.
    [Show full text]
  • Venous Diseases,…
    PHYTOPHARMACEUTICALS academic year 2018/19 LECTURE 6 – Preparations used to treat some circulatory disorders, venous diseases,… Dr. Ivana Daňková Dept. of Natural Drugs, Faculty of Pharmacy, VFU Brno PHYTOPHARMACEUTICALS in the treatment of some CIRCULATORY DISORDERS Circulatory disorders is any disorder or condition that affects circulatory system Circulatory disorders can arise from problems with the heart, blood vessels or the blood itself. Disorders of the circulatory system generally result in diminished flow of blood and oxygen supply to the tissues. They can be classified into 5 groups: traumatic, compressive, occlusive, tumors/malformations and vasospastic (spasm of the artery, which reduces its diameter and thus its blood flow) 2 PHYTOPHARMACEUTICALS in the treatment of some CIRCULATORY DISORDERS Peripheral vascular diseases (PVDs) are circulation disorders that affect blood vessels outside of the heart and brain. PVD typically strikes the veins and arteries that supply „lower body“, the arms, legs = peripheral vessels. In PVD, blood vessels are narrowed. Narrowing is usually caused by arteriosclerosis = a condition where plaque builds up inside a vessel. It is also called “hardening of the arteries.” Plaque decreases the amount of blood and oxygen supplied to the arms and legs. As plaque growth progresses, clots may develop. This further restricts the affected vessel. Eventually, arteries can become obstructed. 3 PHYTOPHARMACEUTICALS in the treatment of some CIRCULATORY DISORDERS PVD that develops only in the arteries
    [Show full text]
  • Method Development and Validation for the Simultaneous Quantitative Estimation of Calcium Dobesilate and Troxerutin in Tablets by Reverse Phase Hplc
    International Journal of Pharmacy and Pharmaceutical Sciences Academic Sciences ISSN- 0975-1491 Vol 6 suppl 2, 2014 Research Article METHOD DEVELOPMENT AND VALIDATION FOR THE SIMULTANEOUS QUANTITATIVE ESTIMATION OF CALCIUM DOBESILATE AND TROXERUTIN IN TABLETS BY REVERSE PHASE HPLC N.J.R. HEPSEBAH, P. PADMA, A.ASHOK KUMAR* Department of Pharmaceutical analysis and Quality Assurance, Vijayacollege of pharmacy, Munaganur (village), Hayathnagar (mandal), Hyderabad 501511, India. Email: [email protected] Received: 10 Nov 2013, Revised and Accepted: 28 Jan 2014 ABSTRACT Objective: To develop a new, simple, precise, accurate, linear and rapid Reverse Phase High Performance Liquid Chromatographic (RP-HPLC) method for the simultaneous quantitative estimation of Calcium dobesilate 500 mg and Troxerutin500 mg in tablets as per ICH guidelines. Methods: The method uses reverse phase column, Enable C18G (250X4.6 mm; 5μ) column and an isocratic elution. Method optimized conditions include a mobile phase of methanol:0.02M potassium dihydrogen orthophosphate buffer adjusted to pH 4 in the proportion of 50:50 v/v, flow rate of 0.8 ml/min and a detection wavelength of 210 nm using a UV detector. Results: The developed method resulted in troxerutin eluting at 7.06 min and calcium dobesilate at 3.5 min. The method precision is exemplified by relative standard deviations of 0.7% for troxerutin and 0.71% for calcium dobesilate. The linearity of the method was over the range 62.5-250μg/ml for both the drugs. Accuracy studies revealed % mean recoveries between 98 and 102 during spiking experiments. The limit of detection was obtained as 3 ng/ml for Calcium dobesilate and 0.5µg/ml for Troxerutin, while the limit of quantitation was obtained as 8ng/ml for Calcium dobesilate and 1µg/ml for Troxerutin.
    [Show full text]
  • VENOUS DISORDERS: More Than a Cosmetic Concern
    Volume 1, No.4 November/December 1998 A CONCISE UPDATE OF IMPORTANT ISSUES CONCERNING NATURAL HEALTH INGREDIENTS Edited By: Thomas G. Guilliams Ph.D. VENOUS DISORDERS: More than a cosmetic concern. For many years, veins have been thought to function only as passageways for blood to flow back into the heart. This has given way in recent years to an understanding that the venous system performs many functions that are vital to the whole circulatory network; such as their capability of constricting and dilating, storing large volumes of blood for use in other areas of the circulation, and even to regulate cardiac output. The alteration of venous blood flow can result in a number of conditions including: Chronic venous insufficiency (CVI), varicose veins, venous thrombosis, pulmonary embolism (a complication of deep vein thrombosis (DVI)), hemorrhoids, lower limb edema, and venous ulcers. These conditions are considered by many to be ‘incurable’. We hope to show here that various natural ingredients have a profound effect on these conditions and their related symptoms. Venous insufficiency has a complex pathology, having a dramatic impact on the quality of life of the patient (1). In fact chronic venous disease of the lower limbs is one of the most common conditions affecting humankind (2), with as many as 8 million Americans suffering from these conditions (3). A recent article reviewed the increasing incidence of deep vein thrombosis and found that between 1966 and 1990 the incidence of DVI was about 1 per 1000 annually, which was “virtually equivalent to the incidence of stroke” (4). While some might think that such problems are simply cosmetic, the underlying pathology can lead to a number of serious consequences.
    [Show full text]